Improved enantioselective hydrogenation of 4-substituted 1,2-dihydroquinolines in presence of a chiral iridium catalyst and an additive

ABSTRACT

The invention relates to a process for preparing optically active 4-substituted 1,2,3,4-tetrahydroquinolines comprising enantioselective hydrogenation of the corresponding 4-substituted 1,2-dihydroquinolines in presence of a chiral iridium (P,N)-ligand catalyst and an additive.

The invention relates to a process for preparing optically active4-substituted 1,2,3,4-tetrahydroquinolines comprising enantioselectivehydrogenation of the corresponding 4-substituted 1,2-dihydroquinolinesin presence of a chiral iridium (P,N)-ligand catalyst and an additive.

It is known from EP 0 654 464 that N-acetyl-tetrahydroquinolines can beconverted to the corresponding 4-aminoindane derivatives via arearrangement reaction.

4-aminoindane derivatives are important intermediates for preparingvarious N-indanyl heteroaryl carboxamides having fungicidal activity (EP0 654 464, WO 2011/162397, WO 2012/084812, WO 2015/197530).

EP 3 103 789 discloses a method for optically resolving1,1,3-trimethyl-4-aminoindane by converting the enantiomeric mixtureinto the diastereomeric salts of D-tartaric acid. (R)- and(S)-1,1,3-trimethyl-4-aminoindane are obtained after separation andbasification of the diastereomeric salts. This reference also disclosesa method for racemizing the undesired enantiomer, so that the wholemethod allows for converting the undesired enantiomer into the desiredenantiomer via several process steps. (R)-1,1,3-trimethyl-4-aminoindaneis an important intermediate for preparing the pyrazole carboxamidefungicide inpyrfluxam.

A method for preparing chiral intermediates of N-indanyl heteroarylcarboxamides via asymmetic synthesis is also known. WO 2015/141564describes a process for preparing optically active 4-substituted1,2,3,4-tetrahydroquinolines, which process comprises the hydrogenationof the corresponding 4-substituted 1,2-dihydroquinolines in presence ofa transition metal catalyst having an optically active ligand. Theasymmetric hydrogenation of the 4-substituted NH-dihydroquinolinesproceeded with moderate conversion rates (up to 62.6%) andenantioselectivity (up to 71.3% ee), whereas N-acetyl-dihydroquinolinesgave even poorer conversion (up to 14%) and enantioselectivity (up to31% ee).

In the light of the prior art described above, it is an object of thepresent invention to provide a process for preparing optically active4-substituted 1,2,3,4-tetrahydroquinolines which process has advantagesover the processes of the prior art. The process should allow thedesired enantiomer to be prepared in high yield and high enantiomericpurity, with few process steps and few purification steps.

The object described above was achieved by a process for preparing acompound of the formula (Ta) or (Ib),

wherein

-   R¹ is selected from the group consisting of C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₃-C₆-cycloalkyl,    C₆-C₁₄-aryl, or C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl, C₃-C₆-cycloalkyl and the C₁-C₆-alkoxy        in the C₁-C₆-alkoxy-C₁-C₆-alkyl moiety, are optionally        substituted by 1 to 3 substituents independently selected from        the group consisting of halogen, C₁-C₄-alkoxy, C₁-C₄-haloalkyl,        C₁-C₄-haloalkoxy and phenyl,    -   wherein the phenyl may be substituted by one to five        substituents selected independently from each other from        halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and        C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy,-   R² and R³ are the same and are selected from the group consisting of    hydrogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl and C₁-C₆-alkoxy-C₁-C₆-alkyl,    or-   R² and R³ together with the carbon which they are bound to, form a    C₃-C₆-cycloalkyl ring, R⁴ is hydrogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,    C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkyl-amino, C₂-C₆-alkenyl,    C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₄-alkyl,    C₂-C₆-alkenyloxy, 9-flurorenylmethyleneoxy, C₆-C₁₄-aryl,    C₆-C₁₄-aryloxy, C₆-C₁₄-aryl-C₁-C₄-alkyloxy or    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₆-C₁₄-aryl as such or as part of a composite        substituent is unsubstituted or substituted by one to five        substituents selected from the group consisting of halogen,        C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy,-   n is 0, 1, 2, 3 or 4,-   each substituent R⁵, if present, is independently selected from the    group consisting of halogen, C₁-C₆-alkyl,-   C₁-C₆-haloalkyl, C₁-C₆-alkoxy, hydroxyl, amino and    —C(═O)—C₁-C₆-alkyl,-   comprising enantioselective hydrogenation of a compound of the    formula (II)

wherein the substituents R¹, R², R³, R⁴, R⁵ and the integer n are eachas defined for the compound of the formula (Ia) or (Ib),in presence of a chiral iridium catalyst,characterized in that the chiral iridium catalyst comprises a chiralligand of the formula (IIIa), (IIIb), (IVa) (IVb), (IXa), or (IXb)

wherein

-   R⁶, R⁷ and R⁸ are independently from one another selected from the    group consisting of hydrogen, halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,    C₁-C₆-alkoxy, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyl,    C₃-C₇-cycloalkyl-C₁-C₄-alkyl, C₆-C₁₄-aryl and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₃-C₇-cycloalkyl and the C₃-C₇-cycloalkyl in the        C₃-C₇-cycloalkyl-C₁-C₄-alkyl moiety are optionally substituted        by 1 to 3 substituents independently selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and        C₁-C₄-haloalkyl and C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety are optionally substituted by one        to five substituents selected from the group consisting of        halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy,        C₁-C₄-haloalkoxy and phenyl, wherein the phenyl again is        unsubstituted or substituted by one to five C₁-C₆-alkyl        substituents,-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino, C₃-C₁₂-cycloalkyl,    C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy and di(C₁-C₆-alkyl)amino, are optionally        substituted by 1 to 3 substituents independently selected from        the group consisting of halogen, C₁-C₄-alkoxy, C₁-C₄-haloalkyl,        C₁-C₄-haloalkoxy and phenyl, wherein the phenyl may be        substituted by one to five substituents selected independently        from each other from halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy,        C₁-C₄-haloalkyl, and C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and C₃-C₁₂-cycloalkyl,        in each case as such or as part of a composite substituent, are        optionally substituted by one to five substituents selected from        the group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy, C₁-C₄-haloalkoxy and phenyl, wherein the phenyl is        unsubstituted or substituted by one to five C₁-C₆-alkyl        substituents or-   R⁹ and R¹⁰ together with the phosphorus atom which they are bound    to, form a phospholane ring, which may be substituted with one or    two C₁-C₆-alkyl groups, or-   R⁹ and R¹⁰ together form

-   -   in which the bonds identified by “x” and “y” are both bound        directly to the phosphorus atom,    -   p and q are independently from one another selected from 0, 1        and 2,    -   R¹¹ and R¹² are independently selected from C₁-C₆-alkyl and        phenyl, which may be substituted by one to five substituents        selected from the group consisting of halogen, C₁-C₄-alkyl,        C₁-C₄-alkoxy and phenyl, which may be substituted by one or two        C₁-C₄-alkyl substituents,

-   m is 1 or 2,

-   A is

-   -   in which the bond identified by * is bound directly to the        phosphorus atom and in which the bond identified by “#” is bound        directly to the oxazoline moiety,

-   R¹³ is C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₃-C₁₂-cycloalkyl,    C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, C₁-C₄-alkyl-C₃-C₇-cycloalkyl,    C₆-C₁₄-aryl or C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy,

-   R¹⁴ and R¹⁵ are independently from one another selected from the    group consisting of hydrogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,    C₃-C₁₂-cycloalkyl, C₃-C₇-cycloalkyl-C₁-C₄-alkyl,    C₁-C₄-alkyl-C₃-C₇-cycloalkyl, C₆-C₁₄-aryl and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy, or

-   R¹⁴ and R¹⁵ together with the carbon which they are bound to, form a    C₅-C₆-cycloalkyl ring,

-   R¹⁶ and R¹⁷ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino, C₃-C₁₂-cycloalkyl,    C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy, C₁-C₆-cycloalkyl and di(C₁-C₆-alkyl)amino, are        optionally substituted by 1 to 3 substituents independently        selected from the group consisting of halogen, C₁-C₄-alkoxy,        C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and phenyl, wherein the phenyl        may be substituted by one to five substituents selected        independently from each other from halogen, C₁-C₄-alkyl, phenyl,        C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl, the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl, the C₆-C₁₄-aryloxy and        C₃-C₁₂-cycloalkyl, in each case as such or as part of a        composite substituent, are optionally substituted by one to five        substituents selected from the group consisting of halogen,        C₁-C₄-alkyl, phenyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and        C₁-C₄-haloalkoxy, or

-   R¹⁶ and R¹⁷ together with the phosphorus atom which they are bound    to, form a phospholane ring, which may be substituted with one or    two C₁-C₆-alkyl groups, or

-   R¹⁶ and R¹⁷ together form

-   -   in which the bonds identified by “x” and “y” are both bound        directly to the phosphorus atom,    -   p and q are independently from one another selected from 0, 1        and 2,    -   R¹¹ and R¹² are independently selected from C₁-C₆-alkyl and        phenyl, which may be substituted by one to five substituents        selected from the group consisting of halogen, C₁-C₄-alkyl,        C₁-C₄-alkoxy and phenyl, which may be substituted by one or two        C₁-C₄-alkyl substituents,

-   R₁₉ are independently selected from phenyl, benzyl, t-butyl,    isopropyl, cyclohexyl,

-   R²⁰ are independently selected from hydrogen, methyl, ethyl,    isopropyl,

-   R²¹ are independently selected from hydrogen, benzyl, methyl, ethyl

-   R²² are independently selected from cyclohexyl, phenyl,    2-methylphenyl, 4-methylphenyl, 2,6-dimethylphenyl,    3,5-dimethylphenyl, 2,4,6-trimethylphenyl, and    in the presence of an additive,    wherein the additive is selected from the group consisting of    Brsnsted acids, Lewis acids, and mixtures thereof.

It has been found, surprisingly, that optically active 4-substituted1,2,3,4-tetrahydroquinolines (Ia and Ib) can be prepared in high yieldsand excellent enantioselectivity by enantioselective hydrogenation ofthe corresponding 4-substituted 1,2-dihydroquinolines (II) in presenceof a chiral iridium (P,N)-ligand catalyst and an additive.

Definitions

In the definitions of the symbols given in the above formulae,collective terms were used, which are generally representative of thefollowing substituents:

Halogen: fluorine, chlorine, bromine or iodine, preferably fluorine,chlorine or bromine, and more preferably fluorine or chlorine.

Alkyl: saturated, straight-chain or branched hydrocarbyl substituentshaving 1 to 6, preferably 1 to 4 carbon atoms, for example (but notlimited to) C₁-C₆-alkyl such as methyl, ethyl, propyl (n-propyl),1-methylethyl (iso-propyl), butyl (n-butyl), 1-methylpropyl (sec-butyl),2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), pentyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl,2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl,1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl. Particularly, saidgroup is a C₁-C₄-alkyl group, e.g. a methyl, ethyl, propyl,1-methylethyl (isopropyl), butyl, 1-methylpropyl (sec-butyl),2-methylpropyl (iso-butyl) or 1,1-dimethylethyl (tert-butyl) group. Thisdefinition also applies to alkyl as part of a composite substituent, forexample C₃-C₆-cycloalkyl-C₁-C₄-alkyl, C₆-C₁₄-aryl-C₁-C₄-alkyl etc.,unless defined elsewhere.

Alkenyl: unsaturated, straight-chain or branched hydrocarbylsubstituents having 2 to 6, preferably 2 to 4 carbon atoms and onedouble bond in any position, for example (but not limited to)C₂-C₆-alkenyl such as vinyl, allyl, (E)-2-methylvinyl,(Z)-2-methylvinyl, isopropenyl, homoallyl, (E)-but-2-enyl,(Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, 2-methylprop-2-enyl,1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl,(Z)-1-methylprop-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl,(E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl,3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl,3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl,(E)-1-methylbut-2-enyl, (Z)-1-methylbut-2-enyl, (E)-3-methylbut-1-enyl,(Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl,(E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl,1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl,(E)-3,3-dimethylprop-1-enyl, (Z)-3,3-dimethylprop-1-enyl, hex-5-enyl,(E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl,(E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl,4-methylpent-4-enyl, 3-methylpent-4-enyl, 2-methylpent-4-enyl,1-methylpent-4-enyl, 4-methylpent-3-enyl, (E)-3-methylpent-3-enyl,(Z)-3-methylpent-3-enyl, (E)-2-methylpent-3-enyl,(Z)-2-methylpent-3-enyl, (E)-1-methylpent-3-enyl,(Z)-1-methylpent-3-enyl, (E)-4-methylpent-2-enyl,(Z)-4-methylpent-2-enyl, (E)-3-methylpent-2-enyl,(Z)-3-methylpent-2-enyl, (E)-2-methylpent-2-enyl,(Z)-2-methylpent-2-enyl, (E)-1-methylpent-2-enyl,(Z)-1-methylpent-2-enyl, (E)-4-methylpent-1-enyl,(Z)-4-methylpent-1-enyl, (E)-3-methylpent-1-enyl,(Z)-3-methylpent-1-enyl, (E)-2-methylpent-1-enyl,(Z)-2-methylpent-1-enyl, (E)-1-methylpent-1-enyl,(Z)-1-methylpent-1-enyl, 3-ethylbut-3-enyl, 2-ethylbut-3-enyl,1-ethylbut-3-enyl, (E)-3-ethylbut-2-enyl, (Z)-3-ethylbut-2-enyl,(E)-2-ethylbut-2-enyl, (Z)-2-ethylbut-2-enyl, (E)-1-ethylbut-2-enyl,(Z)-1-ethylbut-2-enyl, (E)-3-ethylbut-1-enyl, (Z)-3-ethylbut-1-enyl,2-ethylbut-1-enyl, (E)-1-ethylbut-1-enyl, (Z)-1-ethylbut-1-enyl,2-propylprop-2-enyl, 1-propylprop-2-enyl, 2-isopropylprop-2-enyl,1-isopropylprop-2-enyl, (E)-2-propylprop-1-enyl,(Z)-2-propylprop-1-enyl, (E)-1-propylprop-1-enyl,(Z)-1-propylprop-1-enyl, (E)-2-isopropylprop-1-enyl,(Z)-2-isopropylprop-1-enyl, (E)-1-isopropylprop-1-enyl,(Z)-1-isopropylprop-1-enyl, 1-(1,1-dimethylethyl)ethenyl,buta-1,3-dienyl, penta-1,4-dienyl, hexa-1,5-dienyl or methylhexadienyl.Particularly, said group is vinyl or allyl. This definition also appliesto alkenyl as part of a composite substituent unless defined elsewhere.

Alkynyl: straight-chain or branched hydrocarbyl substituents having 2 to8, preferably 2 to 6, and more preferably 2 to 4 carbon atoms and onetriple bond in any position, for example (but not limited to)C₂-C₆-alkynyl, such as ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl,but-2-ynyl, but-3-ynyl, 1-methylprop-2-ynyl, pent-1-ynyl, pent-2-ynyl,pent-3-ynyl, pent-4-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl,1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, hex-1-ynyl,hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 3-methylpent-4-ynyl,2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl,1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl,4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl,1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl,1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl,1,1-dimethylbut-2-ynyl, or 3,3-dimethylbut-1-ynyl group. Particularly,said alkynyl group is ethynyl, prop-1-ynyl, or prop-2-ynyl. Thisdefinition also applies to alkynyl as part of a composite substituentunless defined elsewhere.

Alkylamino: monoalkylamino or dialkylamino, wherein monoalkylaminorepresents an amino radical having one alkyl residue with 1 to 4 carbonatoms attached to the nitrogen atom. Non-limiting examples includemethylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino andtert-butylamino. Wherein dialkylamino represents an amino radical havingtwo independently selected alkyl residues with 1 to 4 carbon atoms eachattached to the nitrogen atom. Non-limiting examples includeN,N-dimethylamino, N,N-diethyl-amino, N,N-diisopropylamino,N-ethyl-N-methylamino, N-methyl-N-n-propylamino,N-isopropyl-N-n-propylamino and N-tert-butyl-N-methylamino.

Alkoxy: saturated, straight-chain or branched alkoxy substituents having1 to 6, more preferably 1 to 4 carbon atoms, for example (but notlimited to) C₁-C₆-alkoxy such as methoxy, ethoxy, propoxy,1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy,1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy,3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy,1,1-dimethylpropoxy, 1,2-dimethylpropoxy, hexoxy, 1-methylpentoxy,2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy,1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy,2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy,1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxyand 1-ethyl-2-methylpropoxy. This definition also applies to alkoxy aspart of a composite substituent unless defined elsewhere.

Cycloalkyl: mono- or polycyclic, saturated hydrocarbyl substituentshaving 3 to 12, preferably 3 to 8 and more preferably 3 to 6 carbon ringmembers, for example (but not limited to) cyclopropyl, cyclopentyl,cyclohexyl and adamantyl. This definition also applies to cycloalkyl aspart of a composite substituent, for exampleC₃-C₆-cycloalkyl-C₁-C₄-alkyl, unless defined elsewhere.

Haloalkyl: straight-chain or branched alkyl substituents having 1 to 6,preferably 1 to 4 carbon atoms (as specified above), in which some orall of the hydrogen atoms in these groups are replaced by halogen atomsas specified above, for example (but not limited to) C₁-C₃-haloalkylsuch as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl,fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl,dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl,1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl,2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and1,1,1-trifluoroprop-2-yl. This definition also applies to haloalkyl aspart of a composite substituent unless defined elsewhere.

Haloalkenyl and haloalkynyl are defined analogously to haloalkyl exceptthat, instead of alkyl groups, alkenyl and alkynyl groups are present aspart of the substituent.

Haloalkoxy: straight-chain or branched alkoxy substituents having 1 to6, preferably 1 to 4 carbon atoms (as specified above), in which some orall of the hydrogen atoms in these groups are replaced by halogen atomsas specified above, for example (but not limited to) C₁-C₃-haloalkoxysuch as chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy,fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy,dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy,1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy,2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy,2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy,2,2,2-trichloroethoxy, pentafluoroethoxy and 1,1,1-trifluoroprop-2-oxy.This definition also applies to haloalkoxy as part of a compositesubstituent, unless defined elsewhere.

Aryl: mono-, bi- or tricyclic aromatic or partially aromaticsubstituents having 6 to 14 carbon atoms, for example (but not limitedto) phenyl, naphthyl, tetrahydronapthyl, indenyl and indanyl. Thebinding to the superordinate general structure can be carried out viaany possible ring member of the aryl residue. Aryl is preferablyselected from phenyl, 1-naphthyl, 2-naphthyl, 9-phenantryl und9-antracenyl. Phenyl is particularly preferred.

The term “enantioselective” as used herein means that one of the twopossible enantiomers of the hydrogenation product, namely the enantiomerof the formula (Ia) or the enantiomer of the formula (Ib), is preferablyformed. The “enantiomeric excess” or “ee” indicates the degree ofenantioselectivity:

${\%{ee}} = {\frac{{{major}{enantiomer}({mol})} - {{minor}{enantiomer}({mol})}}{{{major}{enantiomer}({mol})} + {{minor}{{enantiomer}{}({mol})}}} \times 100\%}$

The major enantiomer can be controlled by the selection of the chiralligand, for example by selecting the chiral ligand of the formula (IIIa)or the opposite enantiomer (the ligand of the formula (IIIb)), orrespectively by selecting the chiral ligand of the formula (IVa) or theopposite enantiomer (the ligand of the formula (IVb)).

The process according to the invention is used for preparing thecompound of the formula (Ta) or (Ib), preferably (Ia).

Preferred are compounds of the formula (Ia) or (Ib), in particular (Ia),wherein the substituents are defined as follows:

-   R¹ is C₁-C₆-alkyl or C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein C₆-C₁₄-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is        unsubstituted or substituted by one to five substituents        selected from the group consisting of halogen, C₁-C₄-alkyl,        C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy-   R² and R³ are the same and are selected from C₁-C₄-alkyl,-   R⁴ is C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,    phenyl or benzyl,-   n is 0, 1 or 2,-   each substituent R⁵, if present, is independently selected from the    group consisting of halogen, C₁-C₆-alkyl and C₁-C₆-haloalkyl.

More preferred are compounds of the formula (Ia) or (Ib), in particular(Ia), wherein the substituents are defined as follows:

-   R¹ is C₁-C₆-alkyl-   R² and R³ are the same and are selected from C₁-C₄-alkyl,-   R⁴ is C₁-C₄-alkyl, C₁-C₄-haloalkyl, phenyl or benzyl,-   n is 0, 1 or 2,-   each substituent R⁵, if present, is independently selected from the    group consisting of halogen and C₁-C₆-alkyl.

Even more preferred are compounds of the formula (Ia) or (Ib), inparticular (Ia), wherein the substituents are defined as follows:

-   R¹ is methyl, ethyl or n-propyl,-   R² and R³ are methyl,-   R⁴ is C₁-C₄-alkyl,-   n is 0, 1 or 2,-   each substituent R⁵, if present, is independently selected from the    group consisting of halogen and C₁-C₆-alkyl.

Most preferred are compounds of the formula (Ia) or (Ib), in particular(Ia), wherein the substituents are defined as follows:

-   R¹ is methyl or n-propyl,-   R² and R³ are methyl,-   R⁴ is methyl,-   n is 0 or 1,-   substituent R⁵, if present, is fluorine.

The process according to the invention comprises enantioselectivehydrogenation of the compound of the formula (II). The substituents R¹,R², R³, R⁴, R⁵ and the integer n in the compound of the formula (II) areeach as defined for the compound of the formula (Ta) or (Ib).

The enantioselective hydrogenation of the compound of the formula (II)is conducted in presence of an additive selected from the groupconsisting of Brsnsted acids, Lewis acids, and mixtures thereof.

In a preferred embodiment of the process according to the invention, theadditive is selected from the group consisting of hexafluorophosphoricacid, acetic acid, trifluoromethylsulfonic acid, water,pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroboricacid, tetrafluoroboric acid diethylether complex, nafion, amberlyst,1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol, triphenylborane,tris[3,5-bis(trifluoro-methyl)phenyl]borane,tris(2,3,4,5,6-pentafluorophenyl)borane, borane tetrahydrofuranecomplex, boric acid, aluminum (III) trifluoromethanesulfonate, zinc (II)trifluoromethanesulfonate, scandium (III) trifluoro-methanesulfonate,aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum,boron trifluoride, complexes of boron trifluoride, and mixtures thereof.

Suitable complexes of boron trifluoride are complexes of borontrifluoride with organic solvents, such as dialkyl ethers or alcohols,and complexes of boron trifluoride with organic acids, such ascarboxylic acids. Preferred boron trifluoride complexes are selectedfrom the group consisting of boron trifluoride-diethylether complex,boron trifluoride acetic acid complex and boron trifluoride n-propanolcomplex.

In a more preferred embodiment of the process according to theinvention, the additive is selected from the group consisting ofhexafluorophosphoric acid, pentafluorophenol,3,5-bis(trifluoromethyl)phenol, tetra-fluoroboric acid diethylethercomplex, triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane,tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum (III)trifluoromethanesulfonate, scandium (III) trifluoro-methanesulfonate,aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum,boron trifluoride, complexes of boron trifluoride, and mixtures thereof,wherein the boron trifluoride complexes are preferably selected from thegroup consisting of boron trifluoride-diethylether complex, borontrifluoride acetic acid complex and boron trifluoride n-propanolcomplex.

In a even more preferred embodiment of the process according to theinvention, the additive is selected from the group consisting ofhexafluorophosphoric acid, pentafluorophenol,3,5-bis(trifluoromethyl)phenol, triphenylborane,tris[3,5-bis(trifluoromethyl)phenyl]borane,tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum (III)trifluoromethanesulfonate, scandium (III) trifluoromethanesulfonate,aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum,boron trifluoride, complexes of boron trifluoride, and mixtures thereof,wherein the boron trifluoride complexes are preferably selected from thegroup consisting of boron trifluoride-diethylether complex, borontrifluoride acetic acid complex and boron trifluoride n-propanolcomplex.

In the most preferred embodiment of the process according to theinvention, the additive is selected from the group consisting ofaluminum (III) trifluoromethanesulfonate, scandium (III)trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane,hexafluorophosphoric acid, boron trifluoride, borontrifluoride-di-ethylether complex, boron trifluoride acetic acid complexand boron trifluoride n-propanol complex.

The amount of additive selected from the group consisting of Brsnstedacids and Lewis acids used is preferably within the range of from 0.1mol % to 10 mol %, more preferably 0.2 mol % to 5 mol %, most preferably0.3 mol % to 2 mol %, in particular 0.4 mol % to 1 mol %, based on theamount of the compound of the formula (II).

The enantioselective hydrogenation of the compound of the formula (II)is conducted in presence of a chiral iridium catalyst comprising achiral ligand of the formula (IIIa), (IIIb), (IVa) or (IVb).

In a preferred embodiment of the process according to the invention, thesubstituents of formulae (Ia), (Ib), (II), (IIIa), (IIIb), (IVa), (IVb),(Ixa) and (Ixb) are defined as follows:

-   R¹ is C₁-C₆-alkyl or C₆-C₁₄-aryl-C₁-C₄-alkyl, wherein C₆-C₁₄-aryl in    the C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is unsubstituted or substituted    by one to five substituents selected from the group consisting of    halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and    C₁-C₄-haloalkoxy-   R² and R³ are the same and are selected from C₁-C₄-alkyl,-   R⁴ is C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,    phenyl or benzyl,-   n is 0, 1 or 2,-   each substituent R⁵, if present, is independently selected from the    group consisting of halogen, C₁-C₆-alkyl and C₁-C₆-haloalkyl,-   R⁶ is C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₃-C₇-cycloalkyl or C₆-C₁₄-aryl,    -   wherein the C₆-C₁₄-aryl is unsubstituted or substituted by one        to five substituents selected from the group consisting of        halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy,        C₁-C₄-haloalkoxy and phenyl, wherein the phenyl again is        unsubstituted or substituted by one to five C₁-C₆-alkyl        substituents,-   R⁷ and R⁸ are independently from one another hydrogen selected from    the group consisting of hydrogen, C₁-C₆-alkyl, C₆-C₁₄-aryl,    C₁-C₆-alkoxy or C₁-C₆-haloalkyl,    -   wherein the C₆-C₁₄-aryl is unsubstituted or substituted by one        to five C₁-C₄-alkyl substituents,-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino,    C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl, C₁-C₆-alkoxy and di(C₁-C₆-alkyl)amino        moieties are optionally substituted by 1 to 3 substituents        independently selected from the group consisting of halogen,        C₁-C₄-alkoxy, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and phenyl,        wherein the phenyl may be substituted by one to five        substituents selected independently from each other from        halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and        C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and C₃-C₁₂-cycloalkyl,        as such or as part of a composite substituent, in each case is        unsubstituted or substituted by one to five substituents        selected from the group consisting of halogen, C₁-C₄-alkyl,        C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy and phenyl,        wherein the phenyl is unsubstituted or substituted by one to        five C₁-C₆-alkyl substituents or-   R⁹ and R¹⁰ together with the phosphorus atom which they are bound    to, form a phospholane ring, which may be substituted with one or    two C₁-C₆-alkyl groups,    -   m is 1 or 2,-   A is

-   -   in which the bond identified by “*” is bound directly to the        phosphorus atom and in which the bond identified by “#” is bound        directly to the oxazoline moiety,

-   R¹³ is C₃-C₆-alkyl, C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl or    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy,

-   R¹⁴ and R¹⁵ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is unsubstituted or substituted        by one to five substituents selected from the group consisting        of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and        C₁-C₄-haloalkoxy, or

-   R¹⁴ and R¹⁵ together with the carbon which they are bound to, form a    C₅-C₆-cycloalkyl ring,

-   R¹⁶ and R¹⁷ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl is optionally substituted by 1 to 3        substituents independently selected from the group consisting of        halogen, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and        phenyl, wherein the phenyl may be substituted by one to five        substituents selected independently from each other from        halogen, C₁-C₄-alkyl, phenyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and        C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy, or

-   R¹⁶ and R¹⁷ together with the phosphorus atom which they are bound    to, form a phospholane ring, which may be substituted with one or    two C₁-C₆-alkyl groups,

-   R¹⁹ is phenyl, t-butyl,

-   R²⁰ is hydrogen, methyl,

-   R²¹ is benzyl, methyl,

-   R²² is cyclohexyl,    and the additive is selected from the group consisting of    hexafluorophosphoric acid, trifluoromethyl sulfonic acid, water,    pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, tetrafluoroboric    acid, tetrafluoroboric acid diethylether complex, nafion, amberlyst,    1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol,    triphenyl-borane, tris[3,5-bis(trifluoromethyl)phenyl]borane,    tris(2,3,4,5,6-pentafluorophenyl)borane, borane tetra-hydrofurane    complex, boric acid, aluminum (III) trifluoromethanesulfonate,    zinc (II) trifluoromethane-sulfonate, scandium (III)    trifluoromethanesulfonate, aluminum (III) fluoride, titanium (IV)    isopropoxide, trimethyl aluminum, boron trifluoride, complexes of    boron trifluoride, and mixtures thereof, wherein the boron    trifluoride complexes are preferably selected from the group    consisting of boron trifluoride-diethylether complex, boron    trifluoride acetic acid complex and boron trifluoride n-propanol    complex.

In a more preferred embodiment of the process according to theinvention, the substituents of formulae (Ia), (Ib), (II), (IIIa),(IIIb), (IVa), (IVb), (IXa), and (IXb) are defined as follows:

-   R¹ is C₁-C₆-alkyl,-   R² and R³ are the same and are selected from C₁-C₄-alkyl,-   R⁴ is C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,    phenyl or benzyl,-   n is 0, 1 or 2,    -   each substituent R⁵, if present, is independently selected from        the group consisting of halogen, C₁-C₆-alkyl and        C₁-C₆-haloalkyl,-   R⁶ is selected from the group consisting of 1-naphtyl, 2-naphtyl,    9-antracenyl, 9-phenantryl or phenyl, which is unsubstituted or    substituted by one to five substituents selected from the group    consisting of halogen, C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl    and phenyl, wherein the phenyl again is unsubstituted or substituted    by one to five C₁-C₆-alkyl substituents,-   R⁷ and R⁸ are independently from one another hydrogen or    C₁-C₆-alkyl,-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl,    tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl, and-   m is 1 or 2,-   A is

-   -   in which the bond identified by “*” is bound directly to the        phosphorus atom and in which the bond identified by “#” is bound        directly to the oxazoline moiety,

-   R¹³ is tert-butyl, iso-propyl or phenyl,

-   R¹⁴ and R¹⁵ are methyl,

-   R¹⁶ and R¹⁷ are each the same and 2-methylphenyl or    3,5-bismethylphenyl, and the additive is selected from the group    consisting of aluminum (III) trifluoromethanesulfonate,    scandium (III) trifluoromethanesulfonate,    tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluorophosphoric acid,    boron trifluoride and complexes of boron trifluoride, wherein the    complexes of boron trifluoride are preferably selected from boron    trifluoride-diethylether complex, boron trifluoride acetic acid    complex and boron trifluoride n-propanol complex,

-   R¹⁹ is phenyl,

-   R²⁰ is methyl,

-   R²¹ is benzyl,

-   R²² is cyclohexyl,    and the additive is selected from the group consisting of    hexafluorophosphoric acid, pentafluorophenol,    3,5-bis(trifluoromethyl)phenol, triphenylborane,    tris[3,5-bis(trifluoromethyl)phenyl]borane,    tris(2,3,4,5,6-penta-fluorophenyl)borane, aluminum (III)    trifluoromethanesulfonate, scandium (III) trifluoromethanesulfonate,    aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl    aluminum, boron trifluoride, complexes of boron trifluoride, and    mixtures thereof, wherein the complexes of boron trifluoride are    preferably selected from boron trifluoride-diethylether complex,    boron trifluoride acetic acid complex and boron trifluoride    n-propanol complex.

In the most preferred embodiment of the process according to theinvention, the substituents of formulae (Ia), (Ib), (II), (IIIa), (IIIb)are defined as follows:

-   R¹ is C₁-C₄-alkyl,-   R² and R³ are methyl,-   R⁴ is C₁-C₄-alkyl,-   n is 0 or 1-   R⁵ if present, is fluorine,-   R⁶ phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl,    4-tert-butylphenyl, 4-methoxyphenyl,    3,5-bis-tert-butyl-4-methoxyphenyl, 4-tert-butyl-2,6-dimethylphenyl,    4-fluorophenyl, 4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl    2,4,6-triisopropylphenyl, 9-phenantryl or    2,6-diethyl-4-methylphenyl,-   R⁷ is hydrogen,-   R⁸ is hydrogen or methyl,-   R⁹ and R¹⁰ are each the same and selected from the group consisting    of ethyl, iso-propyl, tert-butyl, cyclopentyl, adamantyl and    cyclohexyl,-   m is 1.

In a preferred embodiment of the process according to the invention, theligand of the formula (IIIa) or (IIIb) is used. Depending on whethercompound (Ia) or (Ib) is the desired product, the ligand of the formula(IIIa) or (IIIb) is selected.

Preferred are ligands of the formulae (IIIa) and (IIIb), wherein thesubstituents are defined as follows:

-   R⁶ is C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₃-C₇-cycloalkyl or C₆-C₁₄-aryl,    -   wherein the C₆-C₁₄-aryl is unsubstituted or substituted by one        to five substituents selected from the group consisting of        halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy,        C₁-C₄-haloalkoxy and phenyl, wherein the phenyl again is        unsubstituted or substituted by one to five C₁-C₆-alkyl        substituents,-   R⁷ and R⁸ are independently from one another selected from the group    consisting of hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, C₆-C₁₄-aryl or    C₁-C₆-haloalkyl,    -   wherein the C₆-C₁₄-aryl is unsubstituted or substituted by one        to five C₁-C₄-alkyl substituents,-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino,    C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl, C₁-C₆-alkoxy and di(C₁-C₆-alkyl)amino        moieties are optionally substituted by 1 to 3 substituents        independently selected from the group consisting of halogen,        C₁-C₄-alkoxy, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and phenyl,        wherein the phenyl may be substituted by one to five        substituents selected independently from each other from        halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and        C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryloxy, C₃-C₁₂-cycloalkyl and C₆-C₁₄-aryl,        as such or as part of a composite substituent, in each case is        unsubstituted or substituted by one to five substituents        selected from the group consisting of halogen, C₁-C₄-alkyl,        C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy and phenyl,        wherein the phenyl is unsubstituted or substituted by one to        five C₁-C₆-alkyl substituents or-   R⁹ and R¹⁰ together with the phosphorus atom which they are bound    to, form a phospholane ring, which may be substituted with one or    two C₁-C₆-alkyl groups, and-   m is 1 or 2.

More preferred are ligands of the formulae (IIIa) and (IIIb), whereinthe substituents are defined as follows:

-   R⁶ is selected from the group consisting of 1-naphtyl, 2-naphtyl,    9-antracenyl, 9-phenantryl or phenyl, which is unsubstituted or    substituted by one to five substituents selected from the group    consisting of halogen, C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl    and phenyl, wherein the phenyl again is unsubstituted or substituted    by one to five C₁-C₆-alkyl substituents,-   R⁷ and R⁸ are independently from one another hydrogen or    C₁-C₆-alkyl,-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl,    tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl, and-   m is 1 or 2.

Most preferred are ligands of the formulae (IIIa) and (IIIb), whereinthe substituents are defined as follows:

-   R⁶ is selected from the group consisting of, phenyl, 2,6- or    3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl,    4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,    4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl,    4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl    2,4,6-triisopropylphenyl, 9-phenantryl or    2,6-diethyl-4-methylphenyl,-   R⁷ is hydrogen-   R⁸ is hydrogen or methyl,-   R⁹ and R¹⁰ are each the same and tert-butyl, cyclopentyl or    cyclohexyl, and m is 1.

In another preferred embodiment of the process according to theinvention, the ligand of the formula (IVa) or (IVb) is used. Dependingon whether compound (Ia) or (Ib) is the desired product, the ligand ofthe formula (IVa) or (IVb) is selected.

Preferred are ligands of the formulae (IVa) and (IVb), wherein thesubstituents are defined as follows:

-   A is

-   -   in which the bond identified by “*” is bound directly to the        phosphorus atom and in which the bond identified by “#” is bound        directly to the oxazoline moiety,

-   R¹³ is C₃-C₆-alkyl, C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl or    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy,

-   R¹⁴ and R¹⁵ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₆-C₁₄-aryl, C₃-C₁₂-cycloalkyl, and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is unsubstituted or substituted        by one to five substituents selected from the group consisting        of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and        C₁-C₄-haloalkoxy, or

-   R¹⁴ and R¹⁵ together with the carbon which they are bound to, form a    C₅-C₆-cycloalkyl ring,

-   R¹⁶ and R¹⁷ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl, C₆-C₁₄-aryl and    C₆-C₁₄-aryl-C₁-C₄-alkyl,    -   wherein the C₁-C₆-alkyl is optionally substituted by 1 to 3        substituents independently selected from the group consisting of        halogen, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and        phenyl, wherein the phenyl may be substituted by one to five        substituents selected independently from each other from        halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and        C₁-C₄-haloalkoxy, and    -   wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in the        C₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted or        substituted by one to five substituents selected from the group        consisting of halogen, C₁-C₄-alkyl, phenyl, C₁-C₄-haloalkyl,        C₁-C₄-alkoxy and C₁-C₄-haloalkoxy, or

-   R¹⁶ and R¹⁷ together with the phosphorus atom which they are bound    to, form a phospholane ring, which may be substituted with one or    two C₁-C₆-alkyl groups.

More preferred are ligands of the formulae (IVa) and (IVb), wherein thesubstituents are defined as follows:

-   A is

-   -   in which the bond identified by “*” is bound directly to the        phosphorus atom and in which the bond identified by “#” is bound        directly to the oxazoline moiety,

-   R¹³ is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or    benzyl,

-   R¹⁴ and R¹⁵ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, and C₆-aryl-C₁-C₄-alkyl,    -   wherein the C₆-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is        unsubstituted or substituted by one to five substituents        selected from the group consisting of halogen and C₁-C₄-alkyl,

-   R¹⁶ and R¹⁷ are independently from one another phenyl, 1-naphthyl or    2-naphthyl,    -   which in each case is unsubstituted or substituted by one to        five C₁-C₄-alkyl substituents

Most preferred are ligands of the formulae (IVa) and (IVb), wherein thesubstituents are defined as follows:

-   A is

-   -   In which the bond identified by “*” is bound directly to the        phosphorus atom and in which the bond identified by “#” is bound        directly to the oxazoline moiety,

-   R¹³ is tert-butyl,

-   R¹⁴ and R¹⁵ are methyl, and

-   R¹⁶ and R¹⁷ are independently from one another phenyl, which is    substituted by one or two methyl, in particular R¹⁶ and R¹⁷ are each    the same and phenyl, which is substituted by one or two methyl or    R¹⁶ and R¹⁷ are each the same and 2-methylphenyl or    3,5-dimethylphenyl.

In another preferred embodiment of the process according to theinvention, the ligand of the formula (IXa) or (IXb) is used. Dependingon whether compound (Ia) or (Ib) is the desired product, the ligand ofthe formula (IXa) or (IXb) is selected.

Preferred are ligands of the formulae (IXa) and (IXb), wherein thesubstituents are defined as follows:

-   R¹⁹ are independently selected from phenyl, benzyl, t-butyl,    isopropyl, cyclohexyl,-   R²⁰ are independently selected from hydrogen, methyl, ethyl,    isopropyl,-   R²¹ are independently selected from hydrogen, benzyl, methyl, ethyl,    and-   R²² are independently selected from cyclohexyl, phenyl,    2-methylphenyl, 4-methylphenyl, 2,6-dimethylphenyl,    3,5-dimethylphenyl, 2,4,6-trimethylphenyl.

More preferred are ligands of the formulae (IXa) and (IXb), wherein thesubstituents are defined as follows:

-   R¹⁹ is phenyl, t-butyl,-   R²⁰ is hydrogen, methyl,-   R²¹ is benzyl, methyl, and-   R²² is cyclohexyl.

Most preferred are ligands of the formulae (IXa) and (IXb), wherein thesubstituents are defined as follows:

-   R¹⁹ is phenyl,-   R²⁰ is methyl,-   R²¹ is benzyl, and-   R²² is cyclohexyl.

Preferably, the chiral iridium catalyst is selected from the groupconsisting of [IrL*(COD)]Y and [IrL*(nbd)]Y, wherein

-   L* is the chiral ligand of the formulae (IIIa), (IIIb), (IVa) or    (IVb),-   COD represents 1,5-cyclooctadiene,-   nbd represents norbornadiene, and-   Y is a non-coordinating anion selected from the group consisting of    [B(R¹⁸)₄]⁻, PF₆ ⁻, SbF₆ ⁻, CF₃SO₃ ⁻, [Al{OC(CF₃)₃}₄]⁻ (formula    (VII)) and Δ-TRISPHAT (formula (VIII))

-   -   wherein R¹⁸ is selected from fluorine and phenyl, which is        unsubstituted or substituted with one to five substituents        selected from C₁-C₄-alkyl, C₁-C₄-haloalkyl and halogen.

More preferred are chiral iridium catalysts of the formulae [IrL*(COD)]Yand [IrL*(nbd)]Y, wherein Y is PF₆, [Al{OC(CF₃)₃}₄]⁻ (formula (VII)) or[B(R¹⁸)₄]⁻, wherein R¹⁸ is phenyl, which is unsubstituted or substitutedwith one to five substituents selected from fluorine andtrifluoromethyl.

Even more preferred are chiral iridium catalysts of the general formulae(Va), (Vb), (VIa) and (VIb)

wherein

-   R⁶ is selected from the group consisting of 1-naphtyl, 2-naphtyl,    9-antracenyl, 9-phenantryl or phenyl,    -   wherein 1-naphtyl, 2-naphtyl, 9-antracenyl, 9-phenantryl and        phenyl are unsubstituted or substituted by one to five        substituents selected from the group consisting of halogen,        C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl and phenyl, wherein        the phenyl again is unsubstituted or substituted by one to five        C₁-C₆-alkyl substituents,-   R⁷ and R⁸ are independently from one another hydrogen, C₁-C₆-alkyl    or C₁-C₆-alkoxy-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl,    tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl,-   m is 1 or 2,-   R¹³ is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or    benzyl,-   R¹⁴ and R¹⁵ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, and C₆-aryl-C₁-C₄-alkyl,    -   wherein the C₆-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is        unsubstituted or substituted by one to five substituents        selected from the group consisting of halogen and C₁-C₄-alkyl,-   R¹⁶ and R¹⁷ are independently from one another phenyl, 1-naphthyl or    2-naphthyl,    -   which in each case is unsubstituted or substituted by one to        five substituents selected from the group consisting of halogen,        C₁-C₄-alkyl and C₁-C₄-haloalkyl, and-   R¹⁸ is phenyl, which is unsubstituted or substituted with one to    five substituents selected from fluorine and C₁-C₄-haloalkyl.

Particularly preferred are chiral iridium catalysts of the generalformulae (Va), (Vb), (VIa) and (VIb), wherein

-   R⁶ is selected from the group consisting of phenyl, 2,6- or    3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl,    4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,    4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl,    4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl,    2,4,6-triisopropylphenyl, 9-phenantryl and    2,6-diethyl-4-methylphenyl,-   R⁷ is hydrogen,-   R⁸ is hydrogen or methyl-   R⁹ and R¹⁰ are each the same and tert-butyl, adamantly, cyclopentyl    or cyclohexyl,-   m is 1,-   R¹³ is tert-butyl,-   R¹⁴ and R¹⁵ are methyl,-   R¹⁶ and R¹⁷ are independently from one another phenyl, which is    substituted by one or two methyl, in particular R¹⁶ and R¹⁷ are each    the same and 2-methylphenyl or 3,5-dimethylphenyl, and-   R¹⁸ is 3,5-bis(trifluoromethyl)phenyl.

Most preferred are chiral iridium catalysts of the general formulae(Va), (Vb), wherein

-   R⁶ is selected from the group consisting of phenyl, 2,6- or    3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl,    4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,    4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl,    4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl,    2,4,6-triisopropylphenyl, 9-phenantryl and    2,6-diethyl-4-methylphenyl,-   R⁷ is hydrogen,-   R⁸ is hydrogen or methyl-   R⁹ and R¹⁰ are each the same and tert-butyl, or cyclohexyl,-   m is 1

The amount of iridium catalyst used is preferably within the range offrom 0.001 mol % to 5 mol %, more preferably 0.002 mol % to 4 mol %,most preferably 0.005 mol % to 3 mol %, in particular 0.01 mol % to 2.0mol %, based on the amount of the compound of the formula (II).

The chiral iridium catalyst may be prepared by methods known in the artfrom an iridium (I) catalyst precursor, such as [Ir(COD)Cl]₂, the chiralligand of the formula (IIIa), (IIIb), (IVa) or (IVb) and an alkali saltof the non-coordinating anion (S. Kaiser et al., Angew. Chem. Int. Ed.2006, 45, 5194-5197; W. J. Drury III et al., Angew. Chem. Int. Ed. 2004,43, 70-74).

Preferably, the process according to the invention is performed in thepresence of a chiral iridium catalyst, wherein the chiral iridiumcatalyst is selected from the group consisting of [IrL*(COD)]Y and[IrL*(nbd)]Y, wherein

L* is the chiral ligand of the formula (IIIa), (IIIb), (IVa) or (IVb),

COD represents 1,5-cyclooctadiene,

nbd represents norbornadiene, and

Y is a non-coordinating anion selected from the group consisting of[B(R¹⁸)₄]⁻, PF₆ ⁻, SbF₆ ⁻, CF₃SO₃ ⁻, [Al{OC(CF₃)₃}₄]⁻ (formula (VII))and Δ-TRISPHAT (formula (VIII))

-   -   wherein R¹⁸ is selected from fluorine and phenyl, which is        unsubstituted or substituted with one to five substituents        selected from C₁-C₄-alkyl, C₁-C₄-haloalkyl and halogen,        and in the presence of an additive,        wherein the additive is selected from the group consisting of        hexafluorophosphoric acid, acetic acid, trifluoro-methylsulfonic        acid, water, pentafluorophenol, 3,5-bis(trifluoromethyl)phenol,        tetrafluoroboric acid, tetra-fluoroboric acid diethylether        complex, nafion, amberlyst,        1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol,        triphenylborane, tris[3,5-bis(trifluoromethyl)phenyl]borane,        tris(2,3,4,5,6-pentafluorophenyl)borane, borane tetrahydrofurane        complex, boric acid, aluminum (III) trifluoromethanesulfonate,        zinc (II) trifluoro-methanesulfonate, scandium (III)        trifluoromethanesulfonate, aluminum (III) fluoride,        titanium (IV) isopropoxide, trimethyl aluminum, boron        trifluoride, complexes of boron trifluoride, and mixtures        thereof, wherein the complexes of boron trifluoride are        preferably selected from boron trifluoride-diethylether complex,        boron trifluoride acetic acid complex and boron trifluoride        n-propanol complex.

More preferably the process according to the invention is performed inthe presence of a chiral iridium catalyst, wherein the chiral iridiumcatalyst is selected from the group consisting of chiral iridiumcatalyst of the formulae [IrL*(COD)]Y and [IrL*(nbd)]Y, wherein

L* is the chiral ligand of the formula (IIIa), (IIIb), (IVa) or (IVb),COD represents 1,5-cyclooctadiene,nbd represents norbornadiene, andY is PF₆, [Al{OC(CF₃)₃}₄] (formula (VII)) or [B(R¹⁸)₄],

-   -   wherein R¹⁸ is phenyl, which is unsubstituted or substituted        with one to five substituents selected from fluorine and        trifluoromethyl,        and in the presence of an additive,        wherein the additive is selected from the group consisting of        hexafluorophosphoric acid,pentafluorophenol,        3,5-bis(trifluoromethyl)phenol, tetrafluoroboric acid        diethylether complex, triphenylborane,        tris[3,5-bis(trifluoromethyl)phenyl]borane,        tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum (III)        trifluoro-methanesulfonate, scandium (III)        trifluoromethanesulfonate, aluminum (III) fluoride,        titanium (IV) isopropoxide, trimethyl aluminum, boron        trifluoride, complexes of boron trifluoride, and mixtures        thereof, wherein the complexes of boron trifluoride are        preferably selected from boron trifluoride-diethylether complex,        boron trifluoride acetic acid complex and boron trifluoride        n-propanol complex.

Even more preferably the process according to the invention is performedin the presence of a chiral iridium catalyst, wherein the chiral iridiumcatalyst is selected from the group consisting of chiral iridiumcatalyst of the formulae (Va), (Vb), (VIa) and (VIb)

wherein

-   R⁶ is selected from the group consisting of 1-naphtyl, 2-naphtyl,    9-antracenyl, 9-phenantryl or phenyl, wherein 1-naphtyl, 2-naphtyl,    9-antracenyl, 9-phenantryl and phenyl are unsubstituted or    substituted by one to five substituents selected from the group    consisting of halogen, C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl    and phenyl, wherein the phenyl again is unsubstituted or substituted    by one to five C₁-C₆-alkyl substituents,-   R⁷ and R⁸ are independently from one another hydrogen, C₁-C₆-alkyl    or C₁-C₆-alkoxy-   R⁹ and R¹⁰ are independently from one another selected from the    group consisting of ethyl, iso-propyl, sec-butyl, iso-butyl,    tert-butyl, cyclohexyl, cyclopentyl, adamantyl and benzyl,-   m is 1 or 2,-   R¹³ is iso-propyl, sec-butyl, iso-butyl, tert-butyl, phenyl or    benzyl,-   R¹⁴ and R¹⁵ are independently from one another selected from the    group consisting of C₁-C₆-alkyl, and C₆-aryl-C₁-C₄-alkyl,    -   wherein the C₆-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkyl moiety is        unsubstituted or substituted by one to five substituents        selected from the group consisting of halogen and C₁-C₄-alkyl,-   R¹⁶ and R¹⁷ are independently from one another phenyl, 1-naphthyl or    2-naphthyl,    -   which in each case is unsubstituted or substituted by one to        five substituents selected from the group consisting of halogen,        C₁-C₄-alkyl and C₁-C₄-haloalkyl, and-   R¹⁸ is phenyl, which is unsubstituted or substituted with one to    five substituents selected from fluorine and C₁-C₄-haloalkyl,    and in the presence of an additive,    wherein the additive is selected from the group consisting of    hexafluorophosphoric acid, pentafluorophenol,    3,5-bis(trifluoromethyl)phenol, triphenylborane,    tris[3,5-bis(trifluoromethyl)phenyl]borane,    tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum (III)    trifluoromethanesulfonate, scandium (III)    trifluoromethane-sulfonate, aluminum (III) fluoride, titanium (IV)    isopropoxide, trimethyl aluminum, boron trifluoride, complexes of    boron trifluoride, and mixtures thereof, wherein the boron    trifluoride complexes are preferably selected from the group    consisting of boron trifluoride-diethylether complex, boron    trifluoride acetic acid complex and boron trifluoride n-propanol    complex.

Particularly preferably the process according to the invention isperformed in the presence of a chiral iridium catalyst, wherein thechiral iridium catalyst is selected from the group consisting of chiraliridium catalyst of the formulae (Va), (Vb), (VIa) and (VIb), wherein

-   R⁶ is selected from the group consisting of phenyl, 2,6- or    3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl,    4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,    4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl,    4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl,    2,4,6-triisopropylphenyl, 9-phenantryl and    2,6-diethyl-4-methylphenyl,-   R⁷ is hydrogen,-   R⁸ is hydrogen or methyl-   R⁹ and R¹⁰ are each the same and tert-butyl, adamantly, cyclopentyl    or cyclohexyl,-   m is 1 or 2,-   R¹³ is tert-butyl,-   R¹⁴ and R¹⁵ are methyl,-   R¹⁶ and R¹⁷ are independently from one another phenyl, which is    substituted by one or two methyl, in particular R¹⁶ and R¹⁷ are each    the same and 2-methylphenyl or 3,5-dimethylphenyl, and-   R¹⁸ is 3,5-bis(trifluoromethyl)phenyl,    and in the presence of an additive,    wherein the additive is selected from the group consisting of    aluminum (III) trifluoromethanesulfonate, scandium (III)    trifluoromethanesulfonate, tris(2,3,4,5,6-pentafluorophenyl)borane,    hexafluorophosphoric acid, boron trifluoride and complexes of boron    trifluoride, wherein the boron trifluoride complexes are preferably    selected from the group consisting of boron trifluoride-diethylether    complex, boron trifluoride acetic acid complex and boron trifluoride    n-propanol complex.

The process according to the invention comprises enantioselectivehydrogenation of the compound of the formula (II).

Preferably, the hydrogenation is conducted using hydrogen gas at apressure of from 1 to 300 bar, preferably 3 to 200 bar, most preferably20 to 150 bar.

The hydrogenation is preferably conducted at a temperature within therange of from 20° C. to 130° C., more preferably 30° C. to 100° C.

Suitable solvents are halogenated alcohols such as2,2,2,-trifluoroethanol, hexafluoroisopropanol(1,1,1,3,3,3-hexafluoro-2-propanol) and tetrafluoropropanol(2,2,3,3-tetrafluoro-1-propanol), halogenated hydrocarbons, such aschlorobenzene, dichlorobenzene, dichloromethane, chloroform,tetrachloromethane, dichloroethane and trichloroethane, aromatichydrocarbons such as benzene, toluene and xylene, ethers such as diethylether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amylether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethaneand anisole, and esters such as ethyl acetate, isopropyl acetate, andmixtures thereof.

Preferred solvents are selected from the group consisting of2,2,2,-trifluoroethanol, hexafluoroisopropanol, 1,2-dichloroethane,tetrafluoropropanol, 1,4-dioxane, isopropyl acetate, toluene, andmixtures thereof.

More preferred solvents are selected from the group consisting of2,2,2,-trifluoroethanol, hexafluoroisopropanol, 1,2-dichloroethane,tetrafluoropropanol, and mixtures thereof.

Especially preferred are 2,2,2,-trifluoroethanol andhexafluoroisopropanol.

Most preferred is hexafluoroisopropanol.

Abbreviations and Acronyms

a/a Ac Acetyl c-hexane cyclohexane Cy Cyclohexyl DCM dichloromethaneGC-FID Gas chromatography-Flame ionization detector HPLC Highperformance liquid chromatography Et Ethyl Me Methyl n-BuLin-Butyllithium PTFE Polytetrafluoroethylene RT Room temperature SFCSupercritical fluid chromatography THF tetrahydrofurane TfTrifluoromethylsulfonyl TFE 2,2,2-Trifluoroethanol

Preparation of Iridium Catalysts

The ligand precursors (enantiomerically enriched secondary alcohols)were prepared according to known literature procedures like to themethod disclosed in S. Kaiser et al., Angew. Chem. Int. Ed. 2006, 45,5194-5197 or in D. H. Woodmansee Chem. Sci 2010, 1, 72. The ligands andiridium complexes were prepared by a modified procedure based on thesame literature precedents:

Standard Procedures

Procedure of ligand synthesis (under Ar): A solution of alcoholprecursor in THF (0.25 mmol, in 5.0 mL THF) was cooled to −78° C. andn-BuLi (0.1 mL of a 2.5 M n-BuLi solution in hexane; 0.25 mmol; 1 eq.)was added dropwise to the continuously stirred solution. Aftercompletion of the addition the solution was allowed to warm to roomtemperature and was stirred at this temperature for further 30 min. Thesolution was cooled to −78° C. again and R₂PCl (0.25 mmol, 1 eq.) wasadded to the continuously stirred solution. The mixture was allowed towarm to room temperature and subsequently heated to 50° C. and kept atthis temperature overnight.

The theoretical yield of ligand was calculated using ³¹P-NMR and theligand was used for the next step without further purification.

Procedure of complexation (under Ar): To the crude ligand solution wasadded [Ir(COD)₂]BARF(BARF=Tetrakis[3,5-bis(trifluoromethyl)phenyl]-borate) (as a solid, 1eq. based on the theoretical yield). The resulting mixture was heated to50° C. and kept at this temperature for 3 h.

Work-up (under air): After cooling to room temperature the reactionsolution is rotary evaporated onto silica, loaded onto a column ofsilica. Side components were eluted using pentane/diethylether and thedesired complexes subsequently with DCM. The solvent was then evaporatedunder reduced pressure.

The following catalysts were synthesized and characterized:

with m=1 and R¹⁸=3,5-bis(trifluoromethyl)phenyl

TABLE 1 Catalyst R⁶ R⁷ R⁸ R⁹, R¹⁰ Va-1 phenyl H H tert-butyl Va-2 phenylH methyl tert-butyl Vb-3 phenyl H H cyclohexyl Va-4 phenyl H methylcyclohexyl Vb-5 4-tert-butylphenyl H H cyclohexyl Va-64-tert-butylphenyl H methyl cyclohexyl Vb-7 9-antracenyl H H cyclohexylVa-8 9-antracenyl H methyl cyclohexyl Va-9 2,6-dimethylphenyl H methylcyclohexyl Va-10 2,4,6-trimethylphenyl H methyl cyclohexyl Va-113,5-dimethylphenyl H methyl cyclohexyl Va-12 1-naphtyl H methylcyclohexyl Va-13 4-methoxyphenyl H methyl tert-butyl Va-144-fluorophenyl H methyl tert-butyl Va-15 4-(trifluoromethyl)phenyl Hmethyl tert-butyl Va-16 phenyl H methyl cyclopentyl Vb-17 phenyl H Hethyl Va-18 phenyl H methyl isopropyl Va-19 methyl H methyl cyclohexylVa-20 3,5-bis-tert.-butyl,-4-methoxyphenyl H methyl cyclohexyl Va-212,4,6-triisopropylphenyl H methyl cyclohexyl Va-224-tert-butyl-2,6-dimethylphenyl H methyl cyclohexyl Va-23 phenyl H Hadamantyl Va-24 9-phenantryl H methyl cyclohexyl Va-252,6-diethyl-4-methylphenyl H methyl cyclohexyl Va-26*4-tert-butyl-2,6-dimethylphenyl H methyl cyclohexyl *Counteranion is PF₆instead of BARF

Va-2

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (89.5 mg;53% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.26 (dd, J=7.9, 1.7 Hz, 2H),7.81-7.36 (m, 16H), 5.75 (dt, J=8.0, 5.2 Hz, 1H), 5.34-5.29 (m, 1H),4.51 (q, J=5.3, 3.2 Hz, 1H), 4.11 (dq, J=12.5, 7.6, 5.9 Hz, 1H), 3.08(ddd, J=16.6, 10.3, 3.8 Hz, 1H), 2.99-2.70 (m, 2H), 2.61-2.00 (m, 8H),1.92-1.79 (m, 1H), 1.69 (dd, J=14.8, 8.1 Hz, 1H), 1.51 (s, 9H),1.29-1.24 (m, 3H), 1.06 (d, J=14.4 Hz, 9H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ(ppm)=142.09. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ (ppm)=−62.85. HR-MS (ESI) m/zcalcd for C₃₁H₄₄NOPIr [M]+ 670.2790 found 670.2798.

Va-4

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (241 mg; 71%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.38-8.14 (m, 2H), 7.83-7.43 (m, 16H),5.76 (dt, J=7.7, 4.9 Hz, 1H), 4.81 (t, J=7.6 Hz, 1H), 4.70-4.46 (m, 1H),3.56-3.39 (m, 1H), 3.06 (ddd, J=16.7, 10.3, 3.6 Hz, 1H), 2.98-2.73 (m,2H), 2.71-2.57 (m, 1H), 2.44 (s, 3H), 2.41-2.02 (m, 6H), 2.00-1.75 (m,7H), 1.72-1.54 (m, 4H), 1.46-0.94 (m, 13H), 0.72-0.50 (m, 1H). ³¹P-NMR(122 MHz, CD₂Cl₂) δ (ppm)=121.27. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ(ppm)=−62.86. HR-MS (ESI) m/z calcd for C₃₅H₄₈NOPIr [M]+ 722.3103 found722.3116.

Vb-5

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated as an orange solid (261 mg; 74% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.25 (d, J=8.3 Hz, 2H), 7.87 (d, J=8.1Hz, 1H), 7.81-7.64 (m, 11H), 7.56 (s, 4H), 5.74 (dt, J=8.2, 4.6 Hz, 1H),4.95-4.74 (m, 1H), 4.74-4.51 (m, 1H), 3.60-3.45 (m, 1H), 3.23-2.91 (m,2H), 2.90-2.70 (m, 1H), 2.67-2.50 (m, 1H), 2.52-2.23 (m, 4H), 2.28-2.04(m, 3H), 2.04-1.77 (m, 7H), 1.69-1.58 (m, 4H), 1.45-1.26 (m, 17H),1.17-0.95 (m, 4H), 0.68-0.42 (m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ(ppm)=121.12. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ (ppm)=−62.85. HR-MS (ESI) m/zcalcd for C₃₈H₅₄NOPIr [M]+ 764.3572 found 764.3586.

Va-6

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (286 mg; 64%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CDCl₃): δ (ppm)=8.20 (d, J=8.2 Hz, 2H), 7.77-7.69 (m,8H), 7.66 (d, J=8.4 Hz, 2H), 7.53 (d, J=4.9 Hz, 5H), 5.77-5.67 (m, 1H),4.78 (d, J=7.6 Hz, 1H), 4.57 (s, 1H), 3.47 (s, 1H), 3.08-2.89 (m, 1H),2.89-2.66 (m, 2H), 2.59 (p, J=7.4 Hz, 1H), 2.47-1.74 (m, 15H), 1.42 (s,17H), 1.18-0.78 (m, 5H), 0.72-0.48 (m, 1H). ³¹P-NMR (122 MHz, CDCl₃)121.31. ¹⁹F-NMR (282 MHz, CDCl₃) δ=−62.42. HR-MS (ESI): m/z calculatedfor [C₃₉H₅₆NOP193 Ir]+: 778.3729 found 778.3732.

Vb-7

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated after two time purification as an orange solid (151 mg; 36%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.84 (s, 1H), 8.38-8.27 (m, 1H), 8.21(ddt, J=8.5, 1.3, 0.7 Hz, 1H), 8.18-8.02 (m, 2H), 7.83-7.72 (m, 10H),7.72-7.54 (m, 6H), 7.49 (ddd, J=8.8, 6.6, 1.4 Hz, 1H), 7.23-6.96 (m,1H), 5.74-5.54 (m, 1H), 5.26-5.12 (m, 1H), 4.41-4.18 (m, 1H), 3.53-3.15(m, 3H), 2.75-2.61 (m, 2H), 2.59-2.32 (m, 2H), 2.18-1.91 (m, 6H),1.92-1.74 (m, 5H), 1.74-1.56 (m, 2H), 1.48-1.21 (m, 10H), 1.18-0.99 (m,1H), 0.96-0.59 (m, 2H), 0.39-0.15 (m, 1H), 0.06-−0.11 (m, 1H). ³¹P-NMR(122 MHz, CD₂Cl₂) δ (ppm)=120.30. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ(ppm)=−62.87. HR-MS (ESI) m/z calcd for C₄₂H₅₀NOPIr [M]+ 808.3259 found808.3278.

Va-8

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated using DCM (100%) to afford an orange solid (296 mg; 78%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.68 (s, 1H), 8.23-7.85 (m, 3H),7.75-7.23 (m, 17H), 7.05 (dq, J=8.8, 1.0 Hz, 1H), 5.61-5.40 (m, 2H),5.12-4.88 (m, 1H), 4.24-4.00 (m, 1H), 3.25-2.88 (m, 3H), 2.58-2.46 (m,2H), 2.44-2.14 (m, 7H), 2.08-1.61 (m, 11H), 1.61-1.37 (m, 5H), 1.37-1.07(m, 6H), 1.03-0.85 (m, 1H), 0.65-0.45 (m, 1H), 0.16 (dtd, J=15.8, 10.4,5.6 Hz, 1H), −0.16 (dt, J=13.2, 9.1 Hz, 1H). ³¹P-NMR (122 MHz, CD2Cl2)δ=120.57. ¹⁹F-NMR (282 MHz, CD2Cl2) δ=−62.86. HR-MS (ESI) m/z calcd forC₄₃H₅₂NOPIr [M]+ 822.3416 found 822.3416.

Va-9

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated as an orange solid (298 mg; 82% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.80-7.52 (m, 12H), 7.42-7.19 (m, 3H),7.12 (d, J=7.5 Hz, 1H), 5.65 (td, J=5.6, 2.6 Hz, 1H), 5.48-5.42 (m, 1H),4.43-4.37 (m, 1H), 3.38-3.30 (m, 1H), 3.21-2.89 (m, 3H), 2.67 (s, 3H),2.58-2.45 (m, 2H), 2.42 (s, 3H), 2.38-2.16 (m, 2H), 2.13-2.05 (m, 3H),2.02-1.89 (m, 4H), 1.84 (s, 3H), 1.81-1.72 (m, 2H), 1.64-1.49 (m, 3H),1.39-1.19 (m, 8H), 1.12-0.99 (m, 4H), 0.68-0.56 (m, 1H). ³¹P-NMR (122MHz, CD₂Cl₂) 6=118.80. ¹⁹F-NMR (282 MHz, CD₂Cl₂) 6=−62.88. HR-MS (ESI)m/z calcd for C₃₇H₅₂NOPIr [M]+ 750.3416 found 750.3420.

Va-10

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated as an orange solid (148 mg; 40% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.91-7.46 (m, 12H), 7.21 (s, 1H), 7.09(s, 1H), 6.94 (s, 1H), 5.67-5.63 (m, 1H), 5.46-5.41 (m, 1H), 4.38-4.36(m, 1H), 3.36-3.32 (m, 1H), 3.19-2.85 (m, 3H), 2.64 (s, 3H), 2.53-2.46(m, 2H), 2.41 (s, 3H), 2.35 (s, 3H), 2.31-2.18 (m, 2H), 2.19-1.83 (m,14H), 1.68-1.54 (m, 6H), 1.38-1.20 (m, 5H), 1.14-0.97 (m, 5H), 0.68-0.56(m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ=118.64. ¹⁹F-NMR (282 MHz, CD₂Cl₂)δ=−62.87. HR-MS (ESI) m/z calcd for C₃₈H₅₄NOPIr [M]+ 764.3572 found764.3577.

Va-11

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated using DCM (100%) to afford an orange solid (310 mg; 85%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.86 (s, 2H), 7.79-7.47 (m, 13H), 7.36(s, 1H), 5.79-5.62 (m, 1H), 4.78-4.74 (m, 1H), 4.57-4.53 (m, 1H),3.56-3.48 (m, 1H), 3.13-2.95 (m, 1H), 2.95-2.61 (m, 3H), 2.51 (s, 6H),2.47-2.36 (m, 5H), 2.34-2.03 (m, 5H), 2.03-1.77 (m, 7H), 1.71-1.47 (m,7H), 1.45-1.19 (m, 5H), 1.19-0.98 (m, 4H), 0.70-0.62 (m, 1H). ³¹P-NMR(122 MHz, CD₂Cl₂) δ=121.65. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ=−62.88. HR-MS(ESI) m/z calcd for C₃₇H₅₂NOPIr [M]+ 750.3416 found 750.3406.

Va-12

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated as an orange solid (286 mg; 78% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.61-8.48 (m, 1H), 8.28-8.15 (m, 1H),8.11-7.98 (m, 1H), 7.98-7.81 (m, 1H), 7.79-7.50 (m, 16H), 5.70 (ddd,J=8.1, 4.9, 3.2 Hz, 1H), 5.37-5.25 (m, 1H), 4.79 (d, J=10.4 Hz, 1H),3.53-3.41 (m, 1H), 3.13 (ddd, J=17.2, 9.5, 4.9 Hz, 1H), 2.96 (ddd,J=17.1, 9.4, 4.9 Hz, 1H), 2.88-2.66 (m, 1H), 2.49-2.34 (m, 7H),2.27-2.14 (m, 1H), 2.09-1.56 (m, 15H), 1.43-1.12 (m, 9H), 1.06-0.92 (m,1H), 0.78-0.59 (m, 1H), 0.42-0.25 (m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂)δ=121.69. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ=−62.87. HR-MS (ESI) m/z calcd forC₃₉H₅₀NOPIr [M]+ 722.3259 found 722.3262.

Va-13

The reaction was performed according to the above described standardprocedure. The theoretical yield of the ligand was 51%. The complexcould be isolated as an orange solid (78.0 mg; 39% based on[Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CDCl₃): δ (ppm)=8.22 (d, J=8.7 Hz, 2H), 7.80-7.63 (m,8H), 7.63-7.43 (m, 5H), 7.16 (d, J=8.8 Hz, 2H), 5.82-5.66 (m, 1H),5.37-5.22 (m, 1H), 4.56-4.41 (m, 1H), 4.18-4.00 (m, 1H), 3.93 (s, 3H),3.12-2.97 (m, 1H), 2.96-2.74 (m, 2H), 2.70-2.56 (m, 1H), 2.43 (s, 3H),2.41-2.03 (m, 4H), 1.96-1.84 (m, 1H), 1.72 (dd, J=14.6, 7.9 Hz, 1H),1.51 (d, J=15.0 Hz, 9H), 1.34-1.23 (m, 3H), 1.05 (d, J=14.4 Hz, 9H).³¹P-NMR (122 MHz, CD₂Cl₂) δ (ppm)=141.86. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ(ppm)=−62.85. HR-MS (ESI) m/z calcd for C₃₂H₄₆NO₂PIr [M]+ 700.2895 found700.2899.

Va-14

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)²]BARF (0.225 mmol). The complex couldbe isolated as an orange solid (245 mg; 70% based on [Ir(COD)²]BARF).

¹H-NMR (300 MHz, CDCl₃): δ (ppm)=8.38-8.12 (m, 2H), 7.82-7.63 (m, 8H),7.51 (s, 5H), 7.44-7.17 (m, 2H), 5.81-5.63 (m, 1H), 4.81-4.67 (m, 1H),4.67-4.49 (m, 1H), 3.57-3.35 (m, 1H), 3.05-2.90 (m, 1H), 2.88-2.61 (m,3H), 2.36 (s, 3H), 2.31-2.04 (m, 7H), 2.01-1.73 (m, 7H), 1.70-1.48 (m,6H), 1.42-1.20 (m, 6H), 1.16-0.97 (m, 4H), 0.63-0.40 (m, 1H). ³¹P-NMR(122 MHz, CDCl₃) δ (ppm)=121.31. ¹⁹F-NMR (282 MHz, CDCl₃) δ(ppm)=−62.43, −106.61. HR-MS (ESI) m/z calcd for C₃₅H₄₇NOFPIr [M]+740.3009 found 740.3013.

Va-15

The reaction was performed according to the above described standardprocedure using 287 mg of [Ir(COD)₂]BARF (0.225 mmol). The complex couldbe isolated as an orange solid (180.0 mg; 48% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.46 (d, J=7.9 Hz, 2H), 7.94 (d, J=8.0Hz, 2H), 7.82-7.38 (m, 13H), 5.83-5.69 (m, 1H), 4.94-4.78 (m, 1H),4.73-4.54 (m, 1H), 3.65-3.38 (m, 1H), 3.15-2.72 (m, 3H), 2.61-2.27 (m,7H), 2.25-2.04 (m, 4H), 2.04-1.72 (m, 8H), 1.75-1.58 (m, 3H), 1.43-1.22(m, 8H), 1.19-0.93 (m, 1H), 0.63-0.44 (m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂)δ (ppm)=121.74. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ (ppm)=−62.88, −63.40. HR-MS(ESI) m/z calcd for C₃₆H₄₇NOF₃PIr [M]+ 790.2977 found 790.2990.

Va-16

The reaction was performed according to the above described standardprocedure. The theoretical yield of the ligand was 90%. The complexcould be isolated as an orange solid (261 mg; 75% based on[Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=8.28-8.11 (m, 2H), 7.93-7.45 (m, 16H),5.81 (dt, J=9.3, 5.0 Hz, 1H), 4.89 (t, J=6.9 Hz, 1H), 4.72-4.51 (m, 1H),3.86-3.66 (m, 1H), 3.18-3.04 (m, 1H), 3.04-2.57 (m, 4H), 2.49 (s, 3H),2.46-1.61 (m, 18H), 1.56-1.36 (m, 5H), 1.36-1.14 (m, 1H), 1.13-0.93 (m,1H), 0.77-0.66 (m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ (ppm)=129.37.¹⁹F-NMR (282 MHz, CD₂Cl₂) δ (ppm)=−62.88. HR-MS (ESI) m/z calcd forC₃₃H₄₄NOPIr [M]+ 694.2790 found 694.2789.

Vb-17

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (134 mg; 95%purity based on 31P-NMR; 39% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CDCl₃): δ (ppm)=8.00-7.92 (m, 2H), 7.81-7.76 (m, 1H),7.75-7.64 (m, 10H), 7.62-7.55 (m, 2H), 7.52 (d, J=1.9 Hz, 4H), 5.88 (dt,J=8.3, 4.9 Hz, 1H), 4.52 (dt, J=8.3, 4.2 Hz, 1H), 4.37 (ddt, J=7.4, 5.0,2.5 Hz, 1H), 3.61 (td, J=8.0, 3.8 Hz, 1H), 3.17-2.64 (m, 4H), 2.34-1.79(m, 9H), 1.68-1.55 (m, 1H), 1.36-0.90 (m, 9H). ³¹P-NMR (122 MHz, CDCl₃)δ=116.36 (mayor product; 95%), 111.79 (minor species; 5%). ¹⁹F-NMR (282MHz, CDCl₃) δ=−62.41. HR-MS (ESI) m/z calcd for C₂₆H₃₄NOPIr [M]+600.2006 found 600.2006.

Va-18

The reaction was performed (0.5 mmol scale) according to the abovedescribed standard procedure, but after the addition of ClP(iPr)₂ wascompleted, the reaction mixture was stirred at RT for 16 h. The complexcould be isolated as an orange solid (605 mg; 85% based on[Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CDCl₃): δ (ppm)=8.17 (dd, J=7.1, 1.8 Hz, 2H), 7.78-7.40(m, 16H), 5.74 (dt, J=9.0, 4.7 Hz, 1H), 4.83 (t, J=6.9 Hz, 1H), 4.61(dt, J=8.7, 4.1 Hz, 1H), 3.62-3.53 (m, 1H), 3.11-2.94 (m, 1H), 2.91-2.67(m, 2H), 2.67-2.44 (m, 2H), 2.39 (s, 3H), 2.36-1.93 (m, 6H), 1.85 (dd,J=14.5, 7.3 Hz, 1H), 1.46 (dd, J=15.2, 7.1 Hz, 3H), 1.39-1.31 (m, 1H),1.23 (dd, J=13.3, 6.9 Hz, 4H), 1.08 (dd, J=19.4, 7.1 Hz, 3H), 0.52 (dd,J=15.5, 7.1 Hz, 3H). ³¹P-NMR (122 MHz, CDCl₃) δ (ppm)=129.53. ¹⁹F-NMR(282 MHz, CDCl₃) δ (ppm)=−62.42. HR-MS (ESI) m/z calcd for C₂₉H₄₀NOPIr[M]+ 642.2477 found 642.2480.

Va-19

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (249 mg; 73%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.81-7.61 (m, 9H), 7.56 (d, J=2.0 Hz,4H), 7.34 (d, J=8.0 Hz, 1H), 5.76 (dt, J=8.7, 4.5 Hz, 1H), 5.05-4.84 (m,2H), 3.74-3.57 (m, 1H), 3.56-3.36 (m, 1H), 3.07 (s, 3H), 3.01-1.49 (m,23H), 1.42-1.01 (m, 9H), 0.85-0.70 (m, 1H), 0.51-0.25 (m, 1H). ³¹P-NMR(122 MHz, CD₂Cl₂) δ (ppm)=126.20. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ(ppm)=−62.88. HR-MS (ESI) m/z calcd for C₂₉H₄₄NOPIr [M]+ 644.2766 found644.2762.

Va-20

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (164 mg; 42%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.86-7.62 (m, 10H), 7.56 (s, 4H), 7.38(s, 1H), 5.72 (dt, J=8.1, 5.2 Hz, 1H), 4.85-4.63 (m, 2H), 3.80 (s, 3H),3.49-3.30 (m, 1H), 3.18-2.60 (m, 4H), 2.54-2.23 (m, 6H), 2.23-1.57 (m,16H), 1.53-1.49 (m, 20H), 1.46-0.93 (m, 10H). ³¹P-NMR (122 MHz, CD₂Cl₂)δ (ppm)=123.26. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ (ppm)=−62.87. HR-MS (ESI)m/z calcd for C₄₄H₆₆NO₂PIr [M]+ 864.4460 found 864.4448.

Va-21

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (51 mg; 14%based on [Ir(COD)₂]BARF).

¹H-NMR (400 MHz, CD₂Cl₂): δ (ppm)=7.80-7.64 (m, 8H), 7.56 (s, 4H), 7.23(s, 2H), 7.04 (s, 1H), 5.65 (dt, J=5.9, 3.7 Hz, 1H), 5.45-5.35 (m, 1H),4.04 (ddd, J=8.2, 5.4, 3.6 Hz, 1H), 3.34 (dd, J=11.2, 6.4 Hz, 1H),3.19-3.08 (m, 3H), 3.06-2.89 (m, 2H), 2.56-2.44 (m, 2H), 2.41 (s, 3H),2.33-1.84 (m, 9H), 1.84-1.43 (m, 15H), 1.35-1.24 (m, 12H), 1.23-1.14 (m,5H), 1.09 (dd, J=10.0, 6.8 Hz, 6H), 0.95 (d, J=6.6 Hz, 3H), 0.60-0.46(m, 1H). ³¹P-NMR (162 MHz, CD₂Cl₂) δ (ppm)=119.43. ¹⁹F-NMR (282 MHz,CD₂Cl₂) δ (ppm)=−62.86. HR-MS (ESI) m/z calcd for C₄₄H₆₆NOPIr [M]+848.4511 found 848.4512.

Va-22

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (274 mg; 73%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.79-7.66 (m, 8H), 7.56 (s, 4H), 7.29(s, 1H), 7.23 (s, 1H), 7.13 (s, 1H), 5.65 (td, J=5.9, 2.2 Hz, 1H),5.46-5.40 (m, 1H), 4.42-4.36 (m, 1H), 3.38-3.30 (m, 1H), 3.19-2.86 (m,3H), 2.65 (s, 3H), 2.59-2.44 (m, 2H), 2.42 (s, 3H), 2.38-1.54 (m, 20H),1.46-0.98 (m, 21H), 0.70-0.58 (m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ(ppm)=118.67. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ (ppm)=−62.86. HR-MS (ESI) m/zcalcd for C₄₁H₆₀NOPIr [M]+ 806.4042 found 806.4053.

Va-23

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (15.6 mg;20% based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂) δ=8.43-8.36 (m, 2H), 7.92-7.85 (m, 1H),7.81-7.69 (m, 12H), 7.68-7.53 (m, 4H), 5.73-5.65 (m, 1H), 5.50-5.43 (m,1H), 4.58-4.43 (m, 2H), 3.25-3.12 (m, 1H), 3.08-2.94 (m, 1H), 2.92-2.77(m, 1H), 2.72-1.45 (m, 40H). ¹⁹F-NMR (282 MHz, CDCl₃) δ=−62.42. ³¹P-NMR(122 MHz, CD₂Cl₂) δ=134.32. HR-MS (TOF) m/z calcd for C₄₂H₅₄NOPIr [M]+812.3572 found 812.3578.

Va-24

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (274 mg; 72%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂) δ=8.99-8.77 (m, 3H), 8.04-7.63 (m, 15H), 7.56(s, 4H), 5.72-5.63 (m, 1H), 4.88-4.83 (m, 1H), 4.74-4.68 (m, 1H),3.49-3.40 (m, 1H), 3.27-3.07 (m, 1H), 3.08-2.91 (m, 1H), 2.86-2.74 (m,1H), 2.61-2.36 (m, 6H), 2.19 (ddd, J=15.6, 13.8, 8.1 Hz, 1H), 2.11-1.11(m, 25H), 0.99-0.66 (m, 3H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ=121.93. ¹⁹F-NMR(282 MHz, CD₂Cl₂) δ=−62.86. HR-MS (ESI) m/z calcd for C₄₃H₅₂NOPIr [M]⁺822.3410 found 822.3436.

Va-25

The reaction was performed according to the above described standardprocedure. The complex could be isolated as an orange solid (282 mg; 76%based on [Ir(COD)₂]BARF).

¹H-NMR (300 MHz, CD₂Cl₂): δ (ppm)=7.73 (s, 8H), 7.56 (s, 4H), 7.23 (s,1H), 7.14 (s, 1H), 7.00 (s, 1H), 5.62 (dd, J=8.0, 5.6 Hz, 1H), 5.46-5.39(m, 1H), 4.32 (dd, J=7.4, 3.4 Hz, 1H), 3.36-3.27 (m, 1H), 3.19-3.06 (m,2H), 3.01-2.91 (m, 2H), 2.80 (dq, J=14.9, 7.4 Hz, 1H), 2.59-2.43 (m,2H), 2.43-2.15 (m, 7H), 2.15-0.83 (m, 36H), 0.66-0.48 (m, 1H). ³¹P-NMR(122 MHz, CD₂Cl₂) δ (ppm)=119.00. ¹⁹F-NMR (282 MHz, CD₂Cl₂) δ(ppm)=−62.87. HR-MS (ESI) m/z calcd for C₄₀H₅₈NOPIr [M]+ 792.3880 found792.3903.

Va-26

A solution of the respective alcohol precursor in THF (0.25 mmol, in 5.0mL THF) was cooled to −78° C. and n-BuLi (0.1 mL of a 2.5 M n-BuLisolution in hexane; 0.25 mmol; 1 eq.) was added dropwise to thecontinuously stirred solution. After completion of the addition thesolution was allowed to warm to room temperature and was stirred at thistemperature for further 30 min. The solution was cooled to −78° C. againand Cy₂PCl (0.25 mmol, 1 eq.) was added to the continuously stirredsolution. The mixture was allowed to warm to room temperature andsubsequently heated to 50° C. and kept at this temperature overnight.After the reaction was cooled down to RT, THF was removed and dried invacuum, [Ir(cod)Cl]₂ (0.125 mmol) and DCM (5.0 mL) were added to thetube, stirred at 50° C. for 2 h. Then KPF₆ (0.25 mmol) was added to thereaction mixture and stirred at RT for overnight. The reaction solutionis rotary evaporated onto silica, loaded onto a column of silicaprepared with DCM chromatographed with EtOAc/DCM: 1/10 to afford theorange solid after two times column chromatography (130 mg, 55%).

¹H-NMR (300 MHz, CD₂Cl₂) δ=7.37-7.02 (m, 3H), 5.74-5.56 (m, 1H),5.52-5.46 (m, 1H), 4.47-4.30 (m, 1H), 3.45-3.21 (m, 1H), 3.19-2.92 (m,3H), 2.66 (s, 3H), 2.63-2.48 (m, 2H), 2.44 (s, 3H), 2.40-2.19 (m, 2H),2.16-1.70 (m, 15H), 1.68-1.46 (m, 6H), 1.41-1.28 (m, 13H), 1.18-0.95 (m,5H), 0.71-0.58 (m, 1H). ³¹P-NMR (122 MHz, CD₂Cl₂) δ=118.42, −127.01,−132.85, −138.70, −144.55, −150.39, −156.24, −162.09. ¹⁹F-NMR (376 MHz,CD₂Cl₂) δ=−72.64, −74.52. HR-MS (ESI) m/z calcd for C₄₁H₆₀NOPIr [M]⁺806.4036 found 806.4061.

EXAMPLES

Reactions were performed in metal autoclaves. Reaction mixtures wereanalyzed without workup via HPLC (Chiralpak IC column, 95/5heptane/ethanol, 1 mL/min) or SFC (OZ-H column, 2.5% MeOH insupercritical CO₂, 3 mL/min) chromatography.

The Ir-complex Va-25 (catalyst loading given) and 0.64 g1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified with heptane:water wash+crystallization) were placed in an 8-mL autoclave vialcontaining a PTFE-coated stirring bar. The autoclave vial was closedusing a screw cap with septum and flushed with argon (10 m5).Hexafluoroisopropanol (HFIP, 4 mL) and additive (loading given) wereadded via the septum to the vial. The vial was placed in an argoncontaining autoclave and the autoclave was flushed with argon (10 m).The autoclave was pressurized with hydrogen gas (10 bar) andsubsequently depressurized to atmospheric pressure three times. Afterthis the autoclave was pressurized to 60 bar hydrogen pressure and wasplaced in a suitable alumina block. After heating to 85° C. the reactionwas kept at this temperature for the given time.

After cooling to room temperature and depressurizing, the vial was takenout of the autoclave and the reactions outcome was determined by GC-FIDanalysis (deluted with EtOH) and the enantiomeric excess by HPLCanalysis. Typical values are given.

TABLE 2 Additive Reaction catalyst loading Conversion EnantiomericExample (mol %) time (h) (mol %) GC (% a/a) excess (% ee) 1 — 16 0.0295.3 n.d. 2 — 21 0.02 95.5 n.d. 3 — 3 0.02 55.2 n.d. 4 — 16 0.03 97.6n.d. 5 Pentafluorophenol (1) 16 0.02 97.2 n.d. 61,2,2,6,6-Pentamethylpiperidin (1) 16 0.02 67.1 n.d. 7Nonafluoro-tert-butyl alcohol (1) 16 0.03 96.3 n.d. 8Nonafluoro-tert-butyl alcohol (5) 16 0.03 97.5 n.d. 93,5-bis-trifluorophenol (1) 16 0.02 95.7 n.d. 10 AcOH (1) 16 0.02 96n.d. 11 AcOH (5) 3 0.02 66.5 n.d. 12 AcOH (10) 3 0.02 63.7 n.d. 13 AcOH(20) 3 0.02 54.2 n.d. 14 HPF₆ (1) 3 0.02 >99 n.d. 15 HBF₄*OEt₂ (1) 160.02 90.5 n.d. 16 TfOH (1) 16 0.02 76.9 n.d. 17 Sc(OTf)₃ (1) 3 0.02 >9999 18 BF₃*OEt₂ (1) 3 0.02 98.9 98 19 BH₃*THF (1) 3 0.02 69.8 n.d. 20BF₃*AcOH (1) 3 0.02 >99 n.d. 21 BF₃*n-PrOH (1) 3 0.02 >99 n.d. 22Al(OTf)₃ (1) 3 0.02 >99 n.d. 23 AlF₃ (1) 3 0.02 65.9 n.d. 24 AlMe₃ (1) 30.02 91.1 n.d. 25 Ti(O^(i)Pr)₄ (1) 3 0.02 90.7 n.d. 26 BPh₃ (1) 3 0.0285.4 n.d. 27 B(C₆F₅)₃ (1) 3 0.02 >99 97.6 28 B(C₆F₅)₃ (0.5) 3 0.02 97.3n.d. 29 B(C₆F₅)₃ (0.1) 3 0.02 63.3 n.d. 30 B(OH)₃ (1) 3 0.02 72.7 n.d.

Examples 31-36

The Ir-complex Va-25 (catalyst loading given) and1-(2,2,4-trimethyl-1-quinolyl)ethanone (amount given; purified withheptane: water wash+crystallization) were placed in an 25-mL autoclave.The autoclave was flushed with argon (10 min). Hexafluoroisopropanol(1.33 mL per mmol of 1-(2,2,4-trimethyl-1-quinolyl)ethenone)) andadditive (loading given) were added to the autoclave. The autoclave waspressurized with hydrogen gas (10 bar) and subsequently depressurized toatmospheric pressure three times. After this the autoclave waspressurized to 60 bar hydrogen pressure and was placed in a suitablealumina block. After heating to 85° C. the reaction was kept at thistemperature for the given time. After cooling to room temperature anddepressurizing, the reactions outcome was determined by GC-FID analysis(deluted with EtOH) and the enantiomeric excess by HPLC analysis.

TABLE 3 Scale (amount catalyst Additive of compound Reaction loadingConversion Enantiomeric Example (mol %) (II)) time (h) (mol %) GC (%ala) excess (% ee) 31 —  9 mmol 6 0.01 50.8 n.d. 32 B(C₆F₅)₃ (0.5)  9mmol 20 0.01 85.2 n.d. 33 BF₃*OEt₂ (1) 10 mmol 16 0.01 99.2 n.d. 34Al(OTf)₃ (1) 10 mmol 16 0.01 >99 n.d. 35 HPF₆ (1)  9 mmol 16 0.01 97.3n.d. 36 BF₃*AcOH (1)  9 mmol 16 0.01 98.1 n.d.

Examples 37-54

The Ir-complex (identifier and catalyst loading given) and 0.64 g1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified with heptane:water wash+crystallization) were placed in an 8-mL autoclave vialcontaining a PTFE-coated stirring bar. The autoclave vial was closedusing a screw cap with septum and flushed with argon (10 min).Hexafluoroisopropanol (HFIP, 4 mL) and BF₃*OEt₂ (1 mol % with respect to1-(2,2,4-trimethyl-1-quinolyl)ethanone) were added via the septum to thevial. The vial was placed in an argon containing autoclave and theautoclave was flushed with argon (10 min). The autoclave was pressurizedwith hydrogen gas (10 bar) and subsequently depressurized to atmosphericpressure three times. After this the autoclave was pressurized to 60 barhydrogen pressure and was placed in a suitable alumina block. Afterheating to 85° C. the reaction was kept at this temperature for thegiven time. After cooling to room temperature and depressurizing, thevial was taken out of the autoclave and the reactions outcome wasdetermined by GC-FID analysis (deluted with EtOH) and the enantiomericexcess by HPLC analysis. Typical values are given.

TABLE 4 catalyst Conversion Additive Reaction loading GC EnantiomericExample Catalyst (mol %) time (h) (mol %) ( % a/a) excess (% ee) 37Va-26 — 3 0.02 78.8 98.8 38 Va-26 BF₃*OEt₂ (1) 3 0.02 94.2 99 39 Va-22 —3 0.02 85.2 98.5 40 Va-22 BF₃*OEt₂ (1) 3 0.02 >99 98.7 41 Va-15 — 160.025 9.4 n.d. 42 Va-15 — 16 0.05 34.6 83.2 43 Va-15 BF₃*OEt₂ (1) 160.025 82 89.2 44 Vb-7 — 16.5 0.025 79.5 97.5 45 Vb-7 BF₃*OEt₂ (1) 160.025 >99 98.3 46 Va-9 — 16.5 0.025 81.7 97.9 47 Va-9 BF₃*OEt₂ (1) 160.025 >99 98.8 48 Va-11 — 16.5 0.025 42.2 94.5 49 Va-11 BF₃*OEt₂ (1) 160.025 82.4 97.7 50 Va-21 — 16 0.025 74 98 51 Va-21 BF₃*OEt₂ (1) 160.025 >99 99.4 52 Vb-5 — 16 0.025 64.4 n.d. 53 Vb-5 — 16 0.05 98.4 96.854 Vb-5 BF₃*OEt₂ (1) 16 0.025 >99 97.7

Examples 55-58

The Ir-complex Va-25 (0.02 mol %, 0.6 mol) and 0.64 g1-(2,2,4-trimethyl-1-quinolyl)ethanone (3 mmol, purified with heptane:water wash+crystallization) were placed in an 8-mL autoclave vialcontaining a PTFE-coated stirring bar. The autoclave vial was closedusing a screw cap with septum and flushed with argon (10 min).2,2,2-Trifluoroethanol (TFE, 4 mL) and BF₃*OEt₂ (loading given) wereadded via the septum to the vial. The vial was placed in an argoncontaining autoclave and the autoclave was flushed with argon (10 min).The autoclave was pressurized with hydrogen gas (10 bar) andsubsequently depressurized to atmospheric pressure three times. Afterthis the autoclave was pressurized to 60 bar hydrogen pressure and wasplaced in a suitable alumina block. After heating to 85° C. the reactionwas kept at this temperature for 3 h. After cooling to room temperatureand depressurizing, the vial was taken out of the autoclave and thereactions outcome was determined by GC-FID analysis (deluted with EtOH)and the enantiomeric excess by HPLC analysis. Typical values are given.

TABLE 5 BF₃*OEt₂ Conversion Example (mol %) GC (% a/a) 55 — <1 56 1 8657 3 88 58 5 82

Examples 59 and 60

Iridium catalyst (1) from DE112015001290 T5 is an example of thecatalyst structures of formula (IXb). Also using this catalyst thepresence of BF₃*OEt₂ has a strong influence on conversion and a slightlypositive influence on ee (General conditions: 0.2 mol % catalyst (I)from DE112015001290 T5, 40° C., 30 bar H₂, starting materialconcentration 0.1 M in trifluoroethanol)

TABLE 5 Reaction Conv. ee Example Additive time [%] [%] Example 59-1 — 4 h 33 79 Example 59-2 — 16 h 35 79 Example 60-1 1 mol %  4 h 75 83BF₃*OEt₂ Example 60-2 1 mol % 16 h 80 82 BF₃*OEt₂

1. A process for preparing a compound of formula (Ta) or (Ib),

wherein R¹ is selected from the group consisting of C₁-C₆-alkyl,C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₃-C₆-cycloalkyl,C₆-C₁₄-aryl, or C₆-C₁₄-aryl-C₁-C₄-alkyl, wherein the C₁-C₆-alkyl,C₃-C₆-cycloalkyl and the C₁-C₆-alkoxy in the C₁-C₆-alkoxy-C₁-C₆-alkylmoiety, are optionally substituted by 1 to 3 substituents independentlyselected from the group consisting of halogen, C₁-C₄-alkoxy,C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and phenyl, wherein the phenyl may besubstituted by one to five substituents selected independently from eachother from halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, andC₁-C₄-haloalkoxy, and wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in theC₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted orsubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy andC₁-C₄-haloalkoxy, R² and R³ are the same and are selected from the groupconsisting of hydrogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl andC₁-C₆-alkoxy-C₁-C₆-alkyl, or R² and R³ together with the carbon whichthey are bound to, form a C₃-C₆-cycloalkyl ring, R⁴ is hydrogen,C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,C₁-C₆-alkylamino, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl,C₃-C₆-cycloalkyl-C₁-C₄-alkyl, C₂-C₆-alkenyloxy,9-flurorenylmethyleneoxy, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy,C₆-C₁₄-aryl-C₁-C₄-alkyloxy or C₆-C₁₄-aryl-C₁-C₄-alkyl, wherein theC₆-C₁₄-aryl as such or as part of a composite substituent isunsubstituted or substituted by one to five substituents selected fromthe group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,C₁-C₄-alkoxy and C₁-C₄-haloalkoxy, n is 0, 1, 2, 3 or 4, eachsubstituent R⁵, if present, is independently selected from the groupconsisting of halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy,hydroxyl, amino and —C(═O)—C₁-C₆-alkyl, comprising enantioselectivehydrogenation of a compound of the formula (II)

wherein the substituents R¹, R², R³, R⁴, R and the integer n are each asdefined for the compound of the formula (Ia) or (Ib), in presence of achiral iridium catalyst, wherein the chiral iridium catalyst comprises achiral ligand of formula (IIIa), (IIIb), (IVa), (IVb), (IXa) or (IXb),

wherein R⁶, R⁷ and R⁸ are independently from one another selected fromthe group consisting of hydrogen, halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyl,C₃-C₇-cycloalkyl-C₁-C₄-alkyl, C₆-C₁₄-aryl and C₆-C₁₄-aryl-C₁-C₄-alkyl,wherein the C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyland the C₃-C₇-cycloalkyl in the C₃-C₇-cycloalkyl-C₁-C₄-alkyl moiety areoptionally substituted by 1 to 3 substituents independently selectedfrom the group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy andC₁-C₄-haloalkyl and C₁-C₄-haloalkoxy, and wherein the C₆-C₁₄-aryl andthe C₆-C₁₄-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkyl moiety are optionallysubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy,C₁-C₄-haloalkoxy and phenyl, wherein the phenyl again is unsubstitutedor substituted by one to five C₁-C₆-alkyl substituents, R⁹ and R¹⁰ areindependently from one another selected from the group consisting ofC₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkoxy,di(C₁-C₆-alkyl)amino, C₃-C₁₂-cycloalkyl, C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl,C₆-C₁₄-aryl, C₆-C₁₄-aryloxy and C₆-C₁₄-aryl-C₁-C₄-alkyl, wherein theC₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkoxy anddi(C₁-C₆-alkyl)amino, are optionally substituted by 1 to 3 substituentsindependently selected from the group consisting of halogen,C₁-C₄-alkoxy, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and phenyl, wherein thephenyl may be substituted by one to five substituents selectedindependently from each other from halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy,C₁-C₄-haloalkyl, and C₁-C₄-haloalkoxy, and wherein the C₆-C₁₄-aryl,C₆-C₁₄-aryloxy and C₃-C₁₂-cycloalkyl, in each case as such or as part ofa composite substituent, are optionally substituted by one to fivesubstituents selected from the group consisting of halogen, C₁-C₄-alkyl,C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy and phenyl, wherein thephenyl is unsubstituted or substituted by one to five C₁-C₆-alkylsubstituents or R⁹ and R¹⁰ together with the phosphorus atom which theyare bound to, form a phospholane ring, which may be substituted with oneor two C₁-C₆-alkyl groups, or R⁹ and R¹⁰ together form

in which the bonds identified by “x” and “y” are both bound directly tothe phosphorus atom, p and q are independently from one another selectedfrom 0, 1 and 2, R¹¹ and R¹² are independently selected from C₁-C₆-alkyland phenyl, which may be substituted by one to five substituentsselected from the group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-alkoxyand phenyl, which may be substituted by one or two C₁-C₄-alkylsubstituents, m is 1 or 2, A is

in which the bond identified by “*” is bound directly to the phosphorusatom and in which the bond identified by “#” is bound directly to theoxazoline moiety, R¹³ is C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₃-C₁₂-cycloalkyl, C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl,C₁-C₄-alkyl-C₃-C₇-cycloalkyl, C₆-C₁₄-aryl or C₆-C₁₄-aryl-C₁-C₄-alkyl,wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in theC₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted orsubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy andC₁-C₄-haloalkoxy, R¹⁴ and R¹⁵ are independently from one anotherselected from the group consisting of hydrogen, C₁-C₆-alkyl,C₁-C₆-haloalkyl, C₃-C₁₂-cycloalkyl, C₃-C₇-cycloalkyl-C₁-C₄-alkyl,C₁-C₄-alkyl-C₃-C₇-cycloalkyl, C₆-C₁₄-aryl and C₆-C₁₄-aryl-C₁-C₄-alkyl,wherein the C₆-C₁₄-aryl and the C₆-C₁₄-aryl in theC₆-C₁₄-aryl-C₁-C₄-alkyl moiety in each case is unsubstituted orsubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy andC₁-C₄-haloalkoxy, or R¹⁴ and R¹⁵ together with the carbon which they arebound to, form a C₅-C₆-cycloalkyl ring, R¹⁶ and R¹⁷ are independentlyfrom one another selected from the group consisting of C₁-C₆-alkyl,C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino,C₃-C₁₂-cycloalkyl, C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, C₆-C₁₄-aryl,C₆-C₁₄-aryloxy and C₆-C₁₄-aryl-C₁-C₄-alkyl, wherein the C₁-C₆-alkyl,C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkoxy, C₁-C₆-cycloalkyl anddi(C₁-C₆-alkyl)amino, are optionally substituted by 1 to 3 substituentsindependently selected from the group consisting of halogen,C₁-C₄-alkoxy, C₁-C₄-haloalkyl, C₁-C₄-haloalkoxy and phenyl, wherein thephenyl may be substituted by one to five substituents selectedindependently from each other from halogen, C₁-C₄-alkyl, phenyl,C₁-C₄-alkoxy, C₁-C₄-haloalkyl, and C₁-C₄-haloalkoxy, and wherein theC₆-C₁₄-aryl, the C₆-C₁₄-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkyl, theC₆-C₁₄-aryloxy and C₃-C₁₂-cycloalkyl, in each case as such or as part ofa composite substituent, are optionally substituted by one to fivesubstituents selected from the group consisting of halogen, C₁-C₄-alkyl,phenyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy, or R¹⁶ andR¹⁷ together with the phosphorus atom which they are bound to, form aphospholane ring, which may be substituted with one or two C₁-C₆-alkylgroups, or R¹⁶ and R¹⁷ together form

in which the bonds identified by “x” and “y” are both bound directly tothe phosphorus atom, p and q are independently from one another selectedfrom 0, 1 and 2, and R¹¹ and R¹² are independently selected fromC₁-C₆-alkyl and phenyl, which may be substituted by one to fivesubstituents selected from the group consisting of halogen, C₁-C₄-alkyl,C₁-C₄-alkoxy and phenyl, which may be substituted by one or twoC₁-C₄-alkyl substituents, R¹⁹ are independently selected from phenyl,benzyl, t-butyl, isopropyl, cyclohexyl, R²⁰ are independently selectedfrom hydrogen, methyl, ethyl, isopropyl, R²¹ are independently selectedfrom hydrogen, benzyl, methyl, ethyl, R²² are independently selectedfrom cyclohexyl, phenyl, 2-methylphenyl, 4-methylphenyl,2,6-dimethylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, and inthe presence of an additive, wherein the additive is selected from thegroup consisting of Bronsted acids, Lewis acids, and mixtures thereof.2. The process according to claim 1, wherein the additive is selectedfrom the group consisting of hexafluorophosphoric acid, acetic acid,trifluoromethylsulfonic acid, water, pentafluorophenol,3,5-bis(trifluoromethyl)phenol, tetrafluoroboric acid, tetrafluoroboricacid diethylether complex, nafion, amberlyst,1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-ol, triphenylborane,tris[3,5-bis(trifluoromethyl)phenyl]borane,tris(2,3,4,5,6-pentafluorophenyl)borane, borane tetra-hydrofuranecomplex, boric acid, aluminum (III) trifluoromethanesulfonate, zinc (II)trifluoro-methanesulfonate, scandium (III) trifluoromethanesulfonate,aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum,boron trifluoride, complexes of boron trifluoride, and mixtures thereof.3. The process according to claim 1, wherein the additive is selectedfrom the group consisting of hexafluorophosphoric acid,pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane,tris[3,5-bis(trifluoromethyl)phenyl]borane,tris(2,3,4,5,6-pentafluoro-phenyl)borane, aluminum (III)trifluoromethanesulfonate, scandium (III) trifluoromethane-sulfonate,aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum,boron trifluoride, complexes of boron trifluoride, and mixtures thereof.4. The process according to claim 1, wherein R¹ is C₁-C₆-alkyl, R² andR³ are the same and are selected from C₁-C₄-alkyl, R⁴ is C₁-C₄-alkyl,C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, phenyl or benzyl, n is0, 1 or 2, each substituent R⁵, if present, is independently selectedfrom the group consisting of halogen, C₁-C₆-alkyl and C₁-C₆-haloalkyl,R⁶ is selected from the group consisting of 1-naphtyl, 2-naphtyl,9-antracenyl, 9-phenantryl or phenyl, which is unsubstituted orsubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl andphenyl, wherein the phenyl again is unsubstituted or substituted by oneto five C₁-C₆-alkyl substituents, R⁷ and R⁸ are independently from oneanother hydrogen or C₁-C₆-alkyl, R⁹ and R¹⁰ are independently from oneanother selected from the group consisting of ethyl, iso-propyl,sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl andbenzyl, and m is 1 or 2, A is

in which the bond identified by “*” is bound directly to the phosphorusatom and in which the bond identified by “#” is bound directly to theoxazoline moiety, R¹³ is tert-butyl, iso-propyl or phenyl, R¹⁴ and R¹⁵are methyl, R¹⁶ and R¹⁷ are each the same and 2-methylphenyl or3,5-bismethylphenyl, R¹⁹ is phenyl, t-butyl, R²⁰ is hydrogen, methyl,R²¹ is benzyl, methyl R²² is cyclohexyl, and wherein the additive isselected from the group consisting of hexafluorophosphoric acid,pentafluorophenol, 3,5-bis(trifluoromethyl)phenol, triphenylborane,tris[3,5-bis(trifluoro-methyl)phenyl]borane,tris(2,3,4,5,6-pentafluorophenyl)borane, aluminum (III)trifluoromethane-sulfonate, scandium (III) trifluoromethanesulfonate,aluminum (III) fluoride, titanium (IV) isopropoxide, trimethyl aluminum,boron trifluoride, complexes of boron trifluoride, and mixtures thereof.5. The process according to claim 1, wherein R¹ is C₁-C₄-alkyl, R² andR³ are methyl, R⁴ is C₁-C₄-alkyl, n is 0 or 1 R⁵ if present, isfluorine, And wherein the chiral iridium catalyst comprises a chiralligand of the formula (IIIa) or (IIIb),

wherein R⁶ phenyl, 2,6- or 3,5-dimethylphenyl, 2,4,6-trimethylphenyl,4-tert-butylphenyl, 4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,4-tert-butyl-2,6-dimethyl-phenyl, 4-fluorophenyl,4-trifluoromehtylphenyl, 1-naphtyl, 9-antracenyl2,4,6-triisopropylphenyl, 9-phenantryl or 2,6-diethyl-4-methylphenyl, R⁷is hydrogen, R⁸ is hydrogen or methyl, R⁹ and R¹⁰ are each the same andselected from the group consisting of ethyl, iso-propyl, tert-butyl,cyclopentyl, adamantyl and cyclohexyl, m is 1, R¹⁹ is phenyl, R²⁰ ismethyl, R²¹ is benzyl, R²² is cyclohexyl, and wherein the additive isselected from the group consisting of aluminum (III)trifluoromethanesulfonate, scandium (III) trifluoromethanesulfonate,tris(2,3,4,5,6-pentafluorophenyl)borane, hexafluoro-phosphoric acid,boron trifluoride, boron trifluoride-diethylether complex, borontrifluoride acetic acid complex and boron trifluoride n-propanolcomplex.
 6. The process according to claim 1, wherein R¹ is C₁-C₆-alkylor C₆-C₁₄-aryl-C₁-C₄-alkyl, wherein C₆-C₁₄-aryl in theC₆-C₁₄-aryl-C₁-C₄-alkyl moiety is unsubstituted or substituted by one tofive substituents selected from the group consisting of halogen,C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy, R² andR³ are the same and are selected from C₁-C₄-alkyl, R⁴ is C₁-C₄-alkyl,C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, phenyl or benzyl, n is0, 1 or 2, each substituent R⁵, if present, is independently selectedfrom the group consisting of halogen, C₁-C₆-alkyl and C₁-C₆-haloalkyl.7. The process according to claim 1, wherein R¹ is methyl, ethyl orn-propyl, R² and R³ are methyl, R⁴ is C₁-C₄-alkyl, n is 0, 1 or 2, eachsubstituent R⁵, if present, is independently selected from the groupconsisting of halogen and C₁-C₆-alkyl.
 8. The process according to claim1, wherein the hydrogenation is conducted using hydrogen gas at apressure of from 1 to 300 bar.
 9. The process according to claim 1,wherein the amount of chiral iridium catalyst used is within a range offrom 0.001 mol % to 5 mol %, based on the amount of the compound offormula (II).
 10. The process according to claim 1, wherein thehydrogenation is conducted at a temperature within a range of from 20°C. to 130° C.
 11. The process according to claim 1, wherein thehydrogenation is conducted in presence of a solvent selected from thegroup consisting of 2,2,2,-trifluoroethanol,1,1,1,3,3,3-hexafluoro-2-propanol, 1,2-dichloroethane,tetrafluoropropanol, and mixtures thereof.
 12. The process according toclaim 1, wherein the chiral iridium catalyst has formula (Va), (Vb),(VIa) or (VIb):

wherein R⁶ is selected from the group consisting of 1-naphtyl,2-naphtyl, 9-antracenyl, 9-phenantryl or phenyl, wherein 1-naphtyl,2-naphtyl, 9-antracenyl, 9-phenantryl and phenyl are unsubstituted orsubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl andphenyl, wherein the phenyl again is unsubstituted or substituted by oneto five C₁-C₆-alkyl substituents, R⁷ and R⁸ are independently from oneanother hydrogen or C₁-C₆-alkyl, R⁹ and R¹⁰ are independently from oneanother selected from the group consisting of ethyl, iso-propyl,sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl andbenzyl, m is 1 or 2, R¹³ is iso-propyl, sec-butyl, iso-butyl,tert-butyl, phenyl or benzyl, R¹⁴ and R⁵ are independently from oneanother selected from the group consisting of C₁-C₆-alkyl, andC₆-aryl-C₁-C₄-alkyl, wherein the C₆-aryl in the C₆-C₁₄-aryl-C₁-C₄-alkylmoiety is unsubstituted or substituted by one to five substituentsselected from the group consisting of halogen and C₁-C₄-alkyl, R¹⁶ andR¹⁷ are independently from one another phenyl, 1-naphthyl or 2-naphthyl,which in each case is unsubstituted or substituted by one to fivesubstituents selected from the group consisting of halogen, C₁-C₄-alkyland C₁-C₄-haloalkyl, and R¹⁸ is phenyl, which is unsubstituted orsubstituted with one to five substituents selected from fluorine andC₁-C₄-haloalkyl.
 13. The process according to claim 12, wherein R⁶ isselected from the group consisting of phenyl, 2,6- or3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl,4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl,4-trifluoro-methylphenyl, 1-naphtyl, 9-antracenyl2,4,6-triisopropylphenyl, 9-phenantryl or 2,6-diethyl-4-methylphenyl, R⁷is hydrogen, R⁸ is hydrogen or methyl R⁹ and R¹⁰ are each the same andtert-butyl, adamantly, cyclopentyl or cyclohexyl, m is 1 or 2, R¹³ istert-butyl, R¹⁴ and R¹⁵ are methyl, R¹⁶ and R¹⁷ are independently fromone another phenyl, which is substituted by one or two methyl,optionally R¹⁶ and R¹⁷ are each the same and 2-methylphenyl or3,5-dimethylphenyl, and R¹⁸ is 3,5-bis(trifluoromethyl)phenyl.
 14. Theprocess according to claim 1, wherein the chiral iridium catalystcomprises a chiral ligand of the formula (IIIa) or (IIIb), wherein R⁶ isselected from the group consisting of 1-naphtyl, 2-naphtyl,9-antracenyl, 9-phenantryl or phenyl, which is unsubstituted orsubstituted by one to five substituents selected from the groupconsisting of halogen, C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl andphenyl, wherein the phenyl again is unsubstituted or substituted by oneto five C₁-C₆-alkyl substituents, R⁷ and R⁸ are independently from oneanother hydrogen or C₁-C₆-alkyl, R⁹ and R¹⁰ are independently from oneanother selected from the group consisting of ethyl, iso-propyl,sec-butyl, iso-butyl, tert-butyl, cyclohexyl, cyclopentyl, adamantyl andbenzyl, and m is 1 or
 2. 15. The process according to claim 14, whereinR⁶ is selected from the group consisting of phenyl, 2,6- or3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-tert-butylphenyl,4-methoxyphenyl, 3,5-bis-tert-butyl-4-methoxyphenyl,4-tert-butyl-2,6-dimethylphenyl, 4-fluorophenyl,4-trifluoro-methylphenyl, 1-naphtyl, 9-antracenyl2,4,6-triisopropylphenyl, 9-phenantryl or 2,6-diethyl-4-methylphenyl, R⁷is hydrogen R⁸ is hydrogen or methyl, R⁹ and R¹⁰ are each the same andtert-butyl, cyclopentyl or cyclohexyl, and m is
 1. 16. The processaccording to claim 1, wherein the amount of additive used is within arange of from 0.1 to 10 mol %, based on the amount of the compound offormula (II).